9129767 9BHAPH7Z items 1 0 date desc year Gerwick 18 https://wgerwick.scrippsprofiles.ucsd.edu/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-5f887065517076e8b717e4f29b1b7dd7%22%2C%22meta%22%3A%7B%22request_last%22%3A400%2C%22request_next%22%3A50%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22SEUDTSS4%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Lukowski%20et%20al.%22%2C%22parsedDate%22%3A%222023-08-30%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELukowski%2C%20A.%20L.%2C%20Hubert%2C%20F.%20M.%2C%20Ngo%2C%20T.-E.%2C%20Avalon%2C%20N.%20E.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Moore%2C%20B.%20S.%20%282023%29.%20Enzymatic%20Halogenation%20of%20Terminal%20Alkynes.%20%3Ci%3EJournal%20of%20the%20American%20Chemical%20Society%3C%5C%2Fi%3E%2C%20%3Ci%3E145%3C%5C%2Fi%3E%2834%29%2C%2018716%26%23x2013%3B18721.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Fjacs.3c05750%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Fjacs.3c05750%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Enzymatic%20Halogenation%20of%20Terminal%20Alkynes%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22April%20L.%22%2C%22lastName%22%3A%22Lukowski%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Felix%20M.%22%2C%22lastName%22%3A%22Hubert%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Thuan-Ethan%22%2C%22lastName%22%3A%22Ngo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicole%20E.%22%2C%22lastName%22%3A%22Avalon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bradley%20S.%22%2C%22lastName%22%3A%22Moore%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222023-08-30%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1021%5C%2Fjacs.3c05750%22%2C%22ISSN%22%3A%220002-7863%2C%201520-5126%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fpubs.acs.org%5C%2Fdoi%5C%2F10.1021%5C%2Fjacs.3c05750%22%2C%22collections%22%3A%5B%22IWNPIQDK%22%2C%229BHAPH7Z%22%2C%22WK4TGLLK%22%5D%2C%22dateModified%22%3A%222023-09-13T21%3A33%3A58Z%22%7D%7D%2C%7B%22key%22%3A%22RCMKFL2Z%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Kim%20et%20al.%22%2C%22parsedDate%22%3A%222023-08-07%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EKim%2C%20H.%20W.%2C%20Zhang%2C%20C.%2C%20Reher%2C%20R.%2C%20Wang%2C%20M.%2C%20Alexander%2C%20K.%20L.%2C%20Nothias%2C%20L.-F.%2C%20Han%2C%20Y.%20K.%2C%20Shin%2C%20H.%2C%20Lee%2C%20K.%20Y.%2C%20Lee%2C%20K.%20H.%2C%20Kim%2C%20M.%20J.%2C%20Dorrestein%2C%20P.%20C.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Cottrell%2C%20G.%20W.%20%282023%29.%20DeepSAT%3A%20Learning%20Molecular%20Structures%20from%20Nuclear%20Magnetic%20Resonance%20Data.%20%3Ci%3EJournal%20of%20Cheminformatics%3C%5C%2Fi%3E%2C%20%3Ci%3E15%3C%5C%2Fi%3E%281%29%2C%2071.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1186%5C%2Fs13321-023-00738-4%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1186%5C%2Fs13321-023-00738-4%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22DeepSAT%3A%20Learning%20Molecular%20Structures%20from%20Nuclear%20Magnetic%20Resonance%20Data%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hyun%20Woo%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chen%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raphael%22%2C%22lastName%22%3A%22Reher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mingxun%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kelsey%20L.%22%2C%22lastName%22%3A%22Alexander%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Louis-F%5Cu00e9lix%22%2C%22lastName%22%3A%22Nothias%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yoo%20Kyong%22%2C%22lastName%22%3A%22Han%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hyeji%22%2C%22lastName%22%3A%22Shin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ki%20Yong%22%2C%22lastName%22%3A%22Lee%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kyu%20Hyeong%22%2C%22lastName%22%3A%22Lee%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Myeong%20Ji%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pieter%20C.%22%2C%22lastName%22%3A%22Dorrestein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Garrison%20W.%22%2C%22lastName%22%3A%22Cottrell%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20The%20identification%20of%20molecular%20structure%20is%20essential%20for%20understanding%20chemical%20diversity%20and%20for%20developing%20drug%20leads%20from%20small%20molecules.%20Nevertheless%2C%20the%20structure%20elucidation%20of%20small%20molecules%20by%20Nuclear%20Magnetic%20Resonance%20%28NMR%29%20experiments%20is%20often%20a%20long%20and%20non-trivial%20process%20that%20relies%20on%20years%20of%20training.%20To%20achieve%20this%20process%20efficiently%2C%20several%20spectral%20databases%20have%20been%20established%20to%20retrieve%20reference%20NMR%20spectra.%20However%2C%20the%20number%20of%20reference%20NMR%20spectra%20available%20is%20limited%20and%20has%20mostly%20facilitated%20annotation%20of%20commercially%20available%20derivatives.%20Here%2C%20we%20introduce%20DeepSAT%2C%20a%20neural%20network-based%20structure%20annotation%20and%20scaffold%20prediction%20system%20that%20directly%20extracts%20the%20chemical%20features%20associated%20with%20molecular%20structures%20from%20their%20NMR%20spectra.%20Using%20only%20the%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%201%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20H-%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%2013%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20C%20HSQC%20spectrum%2C%20DeepSAT%20identifies%20related%20known%20compounds%20and%20thus%20efficiently%20assists%20in%20the%20identification%20of%20molecular%20structures.%20DeepSAT%20is%20expected%20to%20accelerate%20chemical%20and%20biomedical%20research%20by%20accelerating%20the%20identification%20of%20molecular%20structures.%22%2C%22date%22%3A%222023-08-07%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1186%5C%2Fs13321-023-00738-4%22%2C%22ISSN%22%3A%221758-2946%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fjcheminf.biomedcentral.com%5C%2Farticles%5C%2F10.1186%5C%2Fs13321-023-00738-4%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222023-09-13T21%3A32%3A12Z%22%7D%7D%2C%7B%22key%22%3A%22YEVT6VEY%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Boyarko%20et%20al.%22%2C%22parsedDate%22%3A%222023-08-04%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EBoyarko%2C%20B.%2C%20Podvin%2C%20S.%2C%20Greenberg%2C%20B.%2C%20Momper%2C%20J.%20D.%2C%20Huang%2C%20Y.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20Bang%2C%20A.%20G.%2C%20Quinti%2C%20L.%2C%20Griciuc%2C%20A.%2C%20Kim%2C%20D.%20Y.%2C%20Tanzi%2C%20R.%20E.%2C%20Feldman%2C%20H.%20H.%2C%20%26amp%3B%20Hook%2C%20V.%20%282023%29.%20Evaluation%20of%20bumetanide%20as%20a%20potential%20therapeutic%20agent%20for%20Alzheimer%26%23x2019%3Bs%20disease.%20%3Ci%3EFrontiers%20in%20Pharmacology%3C%5C%2Fi%3E%2C%20%3Ci%3E14%3C%5C%2Fi%3E%2C%201190402.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3389%5C%2Ffphar.2023.1190402%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3389%5C%2Ffphar.2023.1190402%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Evaluation%20of%20bumetanide%20as%20a%20potential%20therapeutic%20agent%20for%20Alzheimer%5Cu2019s%20disease%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ben%22%2C%22lastName%22%3A%22Boyarko%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sonia%22%2C%22lastName%22%3A%22Podvin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Barry%22%2C%22lastName%22%3A%22Greenberg%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jeremiah%20D.%22%2C%22lastName%22%3A%22Momper%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yadong%22%2C%22lastName%22%3A%22Huang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anne%20G.%22%2C%22lastName%22%3A%22Bang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Luisa%22%2C%22lastName%22%3A%22Quinti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ana%22%2C%22lastName%22%3A%22Griciuc%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Doo%20Yeon%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rudolph%20E.%22%2C%22lastName%22%3A%22Tanzi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Howard%20H.%22%2C%22lastName%22%3A%22Feldman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vivian%22%2C%22lastName%22%3A%22Hook%22%7D%5D%2C%22abstractNote%22%3A%22Therapeutics%20discovery%20and%20development%20for%20Alzheimer%5Cu2019s%20disease%20%28AD%29%20has%20been%20an%20area%20of%20intense%20research%20to%20alleviate%20memory%20loss%20and%20the%20underlying%20pathogenic%20processes.%20Recent%20drug%20discovery%20approaches%20have%20utilized%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20in%20silico%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20computational%20strategies%20for%20drug%20candidate%20selection%20which%20has%20opened%20the%20door%20to%20repurposing%20drugs%20for%20AD.%20Computational%20analysis%20of%20gene%20expression%20signatures%20of%20patients%20stratified%20by%20the%20APOE4%20risk%20allele%20of%20AD%20led%20to%20the%20discovery%20of%20the%20FDA-approved%20drug%20bumetanide%20as%20a%20top%20candidate%20agent%20that%20reverses%20APOE4%20transcriptomic%20brain%20signatures%20and%20improves%20memory%20deficits%20in%20APOE4%20animal%20models%20of%20AD.%20Bumetanide%20is%20a%20loop%20diuretic%20which%20inhibits%20the%20kidney%20Na%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%2B%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20-K%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%2B%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20-2Cl%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cu2212%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20cotransporter%20isoform%2C%20NKCC2%2C%20for%20the%20treatment%20of%20hypertension%20and%20edema%20in%20cardiovascular%2C%20liver%2C%20and%20renal%20disease.%20Electronic%20health%20record%20data%20revealed%20that%20patients%20exposed%20to%20bumetanide%20have%20lower%20incidences%20of%20AD%20by%2035%25%5Cu201370%25.%20In%20the%20brain%2C%20bumetanide%20has%20been%20proposed%20to%20antagonize%20the%20NKCC1%20isoform%20which%20mediates%20cellular%20uptake%20of%20chloride%20ions.%20Blocking%20neuronal%20NKCC1%20leads%20to%20a%20decrease%20in%20intracellular%20chloride%20and%20thus%20promotes%20GABAergic%20receptor%20mediated%20hyperpolarization%2C%20which%20may%20ameliorate%20disease%20conditions%20associated%20with%20GABAergic-mediated%20depolarization.%20NKCC1%20is%20expressed%20in%20neurons%20and%20in%20all%20brain%20cells%20including%20glia%20%28oligodendrocytes%2C%20microglia%2C%20and%20astrocytes%29%20and%20the%20vasculature.%20In%20consideration%20of%20bumetanide%20as%20a%20repurposed%20drug%20for%20AD%2C%20this%20review%20evaluates%20its%20pharmaceutical%20properties%20with%20respect%20to%20its%20estimated%20brain%20levels%20across%20doses%20that%20can%20improve%20neurologic%20disease%20deficits%20of%20animal%20models%20to%20distinguish%20between%20NKCC1%20and%20non-NKCC1%20mechanisms.%20The%20available%20data%20indicate%20that%20bumetanide%20efficacy%20may%20occur%20at%20brain%20drug%20levels%20that%20are%20below%20those%20required%20for%20inhibition%20of%20the%20NKCC1%20transporter%20which%20implicates%20non-NKCC1%20brain%20mechansims%20for%20improvement%20of%20brain%20dysfunctions%20and%20memory%20deficits.%20Alternatively%2C%20peripheral%20bumetanide%20mechanisms%20may%20involve%20cells%20outside%20the%20central%20nervous%20system%20%28e.g.%2C%20in%20epithelia%20and%20the%20immune%20system%29.%20Clinical%20bumetanide%20doses%20for%20improved%20neurological%20deficits%20are%20reviewed.%20Regardless%20of%20mechanism%2C%20the%20efficacy%20of%20bumetanide%20to%20improve%20memory%20deficits%20in%20the%20APOE4%20model%20of%20AD%20and%20its%20potential%20to%20reduce%20the%20incidence%20of%20AD%20provide%20support%20for%20clinical%20investigation%20of%20bumetanide%20as%20a%20repurposed%20AD%20therapeutic%20agent.%22%2C%22date%22%3A%222023-8-4%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3389%5C%2Ffphar.2023.1190402%22%2C%22ISSN%22%3A%221663-9812%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.frontiersin.org%5C%2Farticles%5C%2F10.3389%5C%2Ffphar.2023.1190402%5C%2Ffull%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222023-09-13T21%3A34%3A31Z%22%7D%7D%2C%7B%22key%22%3A%22ZFEWTD5G%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Almaliti%20and%20Gerwick%22%2C%22parsedDate%22%3A%222023-07-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EAlmaliti%2C%20J.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282023%29.%20Methods%20in%20marine%20natural%20product%20drug%20discovery%3A%20what%26%23x2019%3Bs%20new%3F%20%3Ci%3EExpert%20Opinion%20on%20Drug%20Discovery%3C%5C%2Fi%3E%2C%20%3Ci%3E18%3C%5C%2Fi%3E%287%29%2C%20687%26%23x2013%3B691.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1080%5C%2F17460441.2023.2214360%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1080%5C%2F17460441.2023.2214360%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Methods%20in%20marine%20natural%20product%20drug%20discovery%3A%20what%5Cu2019s%20new%3F%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jehad%22%2C%22lastName%22%3A%22Almaliti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222023-07-03%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1080%5C%2F17460441.2023.2214360%22%2C%22ISSN%22%3A%221746-0441%2C%201746-045X%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.tandfonline.com%5C%2Fdoi%5C%2Ffull%5C%2F10.1080%5C%2F17460441.2023.2214360%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222023-06-23T15%3A52%3A05Z%22%7D%7D%2C%7B%22key%22%3A%22ABKEVWSS%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Almaliti%20et%20al.%22%2C%22parsedDate%22%3A%222023-04-06%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EAlmaliti%2C%20J.%2C%20Fajtov%26%23xE1%3B%2C%20P.%2C%20Calla%2C%20J.%2C%20LaMonte%2C%20G.%20M.%2C%20Feng%2C%20M.%2C%20Rocamora%2C%20F.%2C%20Ottilie%2C%20S.%2C%20Glukhov%2C%20E.%2C%20Boura%2C%20E.%2C%20Suhandynata%2C%20R.%20T.%2C%20Momper%2C%20J.%20D.%2C%20Gilson%2C%20M.%20K.%2C%20Winzeler%2C%20E.%20A.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20O%26%23x2019%3BDonoghue%2C%20A.%20J.%20%282023%29.%20Development%20of%20Potent%20and%20Highly%20Selective%20Epoxyketone%26%23x2010%3BBased%20Plasmodium%20Proteasome%20Inhibitors.%20%3Ci%3EChemistry%20%26%23x2013%3B%20A%20European%20Journal%3C%5C%2Fi%3E%2C%20%3Ci%3E29%3C%5C%2Fi%3E%2820%29%2C%20e202203958.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fchem.202203958%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fchem.202203958%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Development%20of%20Potent%20and%20Highly%20Selective%20Epoxyketone%5Cu2010Based%20Plasmodium%20Proteasome%20Inhibitors%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jehad%22%2C%22lastName%22%3A%22Almaliti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pavla%22%2C%22lastName%22%3A%22Fajtov%5Cu00e1%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jaeson%22%2C%22lastName%22%3A%22Calla%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gregory%20M.%22%2C%22lastName%22%3A%22LaMonte%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mudong%22%2C%22lastName%22%3A%22Feng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Frances%22%2C%22lastName%22%3A%22Rocamora%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sabine%22%2C%22lastName%22%3A%22Ottilie%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Evgenia%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Evzen%22%2C%22lastName%22%3A%22Boura%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raymond%20T.%22%2C%22lastName%22%3A%22Suhandynata%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jeremiah%20D.%22%2C%22lastName%22%3A%22Momper%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%20K.%22%2C%22lastName%22%3A%22Gilson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Elizabeth%20A.%22%2C%22lastName%22%3A%22Winzeler%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anthony%20J.%22%2C%22lastName%22%3A%22O%27Donoghue%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222023-04-06%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1002%5C%2Fchem.202203958%22%2C%22ISSN%22%3A%220947-6539%2C%201521-3765%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fchemistry-europe.onlinelibrary.wiley.com%5C%2Fdoi%5C%2F10.1002%5C%2Fchem.202203958%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222023-04-10T22%3A38%3A53Z%22%7D%7D%2C%7B%22key%22%3A%225NLHI6IH%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Shrestha%20et%20al.%22%2C%22parsedDate%22%3A%222023-01-07%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EShrestha%2C%20S.%20K.%2C%20Min%2C%20K.%20H.%2C%20Kim%2C%20S.%20W.%2C%20Kim%2C%20H.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Soh%2C%20Y.%20%282023%29.%20Kalkitoxin%3A%20A%20Potent%20Suppressor%20of%20Distant%20Breast%20Cancer%20Metastasis.%20%3Ci%3EInternational%20Journal%20of%20Molecular%20Sciences%3C%5C%2Fi%3E%2C%20%3Ci%3E24%3C%5C%2Fi%3E%282%29%2C%201207.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fijms24021207%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fijms24021207%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Kalkitoxin%3A%20A%20Potent%20Suppressor%20of%20Distant%20Breast%20Cancer%20Metastasis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Saroj%20Kumar%22%2C%22lastName%22%3A%22Shrestha%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kyung%20Hyun%22%2C%22lastName%22%3A%22Min%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Se%20Woong%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hyoungsu%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yunjo%22%2C%22lastName%22%3A%22Soh%22%7D%5D%2C%22abstractNote%22%3A%22Bone%20metastasis%20resulting%20from%20advanced%20breast%20cancer%20causes%20osteolysis%20and%20increases%20mortality%20in%20patients.%20Kalkitoxin%20%28KT%29%2C%20a%20lipopeptide%20toxin%20derived%20from%20the%20marine%20cyanobacterium%20Moorena%20producens%20%28previously%20Lyngbya%20majuscula%29%2C%20has%20an%20anti-metastatic%20effect%20on%20cancer%20cells.%20We%20verified%20that%20KT%20suppressed%20cancer%20cell%20migration%20and%20invasion%20in%20vitro%20and%20in%20animal%20models%20in%20the%20present%20study.%20We%20confirmed%20that%20KT%20suppressed%20osteoclast-soup-derived%20MDA-MB-231%20cell%20invasion%20in%20vitro%20and%20induced%20osteolysis%20in%20a%20mouse%20model%2C%20possibly%20enhancing%5C%2Finhibiting%20metastasis%20markers.%20Furthermore%2C%20KT%20inhibits%20CXCL5%20and%20CXCR2%20expression%2C%20suppressing%20the%20secondary%20growth%20of%20breast%20cancer%20cells%20on%20the%20bone%2C%20brain%2C%20and%20lungs.%20The%20breast-cancer-induced%20osteolysis%20in%20the%20mouse%20model%20further%20reveals%20that%20KT%20plays%20a%20protective%20role%2C%20judging%20by%20micro-computed%20tomography%20and%20immunohistochemistry.%20We%20report%20for%20the%20first%20time%20the%20novel%20suppressive%20effects%20of%20KT%20on%20cancer%20cell%20migration%20and%20invasion%20in%20vitro%20and%20on%20MDA-MB-231-induced%20bone%20loss%20in%20vivo.%20These%20results%20suggest%20that%20KT%20may%20be%20a%20potential%20therapeutic%20drug%20for%20the%20treatment%20of%20breast%20cancer%20metastasis.%22%2C%22date%22%3A%222023-01-07%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.3390%5C%2Fijms24021207%22%2C%22ISSN%22%3A%221422-0067%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.mdpi.com%5C%2F1422-0067%5C%2F24%5C%2F2%5C%2F1207%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222023-02-17T16%3A48%3A13Z%22%7D%7D%2C%7B%22key%22%3A%222HNHGEZ2%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Mullowney%20et%20al.%22%2C%22parsedDate%22%3A%222023%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EMullowney%2C%20M.%20W.%2C%20Duncan%2C%20K.%20R.%2C%20Elsayed%2C%20S.%20S.%2C%20Garg%2C%20N.%2C%20Van%20Der%20Hooft%2C%20J.%20J.%20J.%2C%20Martin%2C%20N.%20I.%2C%20Meijer%2C%20D.%2C%20Terlouw%2C%20B.%20R.%2C%20Biermann%2C%20F.%2C%20Blin%2C%20K.%2C%20Durairaj%2C%20J.%2C%20Gorostiola%20Gonz%26%23xE1%3Blez%2C%20M.%2C%20Helfrich%2C%20E.%20J.%20N.%2C%20Huber%2C%20F.%2C%20Leopold-Messer%2C%20S.%2C%20Rajan%2C%20K.%2C%20De%20Rond%2C%20T.%2C%20Van%20Santen%2C%20J.%20A.%2C%20Sorokina%2C%20M.%2C%20%26%23x2026%3B%20Medema%2C%20M.%20H.%20%282023%29.%20Artificial%20intelligence%20for%20natural%20product%20drug%20discovery.%20%3Ci%3ENature%20Reviews%20Drug%20Discovery%3C%5C%2Fi%3E%2C%20%3Ci%3E22%3C%5C%2Fi%3E%2811%29%2C%20895%26%23x2013%3B916.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41573-023-00774-7%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41573-023-00774-7%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Artificial%20intelligence%20for%20natural%20product%20drug%20discovery%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%20W.%22%2C%22lastName%22%3A%22Mullowney%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Katherine%20R.%22%2C%22lastName%22%3A%22Duncan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Somayah%20S.%22%2C%22lastName%22%3A%22Elsayed%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Neha%22%2C%22lastName%22%3A%22Garg%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Justin%20J.%20J.%22%2C%22lastName%22%3A%22Van%20Der%20Hooft%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nathaniel%20I.%22%2C%22lastName%22%3A%22Martin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%22%2C%22lastName%22%3A%22Meijer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Barbara%20R.%22%2C%22lastName%22%3A%22Terlouw%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Friederike%22%2C%22lastName%22%3A%22Biermann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kai%22%2C%22lastName%22%3A%22Blin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Janani%22%2C%22lastName%22%3A%22Durairaj%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marina%22%2C%22lastName%22%3A%22Gorostiola%20Gonz%5Cu00e1lez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eric%20J.%20N.%22%2C%22lastName%22%3A%22Helfrich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Florian%22%2C%22lastName%22%3A%22Huber%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Stefan%22%2C%22lastName%22%3A%22Leopold-Messer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kohulan%22%2C%22lastName%22%3A%22Rajan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tristan%22%2C%22lastName%22%3A%22De%20Rond%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jeffrey%20A.%22%2C%22lastName%22%3A%22Van%20Santen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maria%22%2C%22lastName%22%3A%22Sorokina%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marcy%20J.%22%2C%22lastName%22%3A%22Balunas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mehdi%20A.%22%2C%22lastName%22%3A%22Beniddir%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Doris%20A.%22%2C%22lastName%22%3A%22Van%20Bergeijk%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Laura%20M.%22%2C%22lastName%22%3A%22Carroll%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chase%20M.%22%2C%22lastName%22%3A%22Clark%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Djork-Arn%5Cu00e9%22%2C%22lastName%22%3A%22Clevert%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chris%20A.%22%2C%22lastName%22%3A%22Dejong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chao%22%2C%22lastName%22%3A%22Du%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Scarlet%22%2C%22lastName%22%3A%22Ferrinho%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Francesca%22%2C%22lastName%22%3A%22Grisoni%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Albert%22%2C%22lastName%22%3A%22Hofstetter%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Willem%22%2C%22lastName%22%3A%22Jespers%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Olga%20V.%22%2C%22lastName%22%3A%22Kalinina%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Satria%20A.%22%2C%22lastName%22%3A%22Kautsar%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hyunwoo%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tiago%20F.%22%2C%22lastName%22%3A%22Leao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Joleen%22%2C%22lastName%22%3A%22Masschelein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Evan%20R.%22%2C%22lastName%22%3A%22Rees%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raphael%22%2C%22lastName%22%3A%22Reher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniel%22%2C%22lastName%22%3A%22Reker%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Philippe%22%2C%22lastName%22%3A%22Schwaller%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marwin%22%2C%22lastName%22%3A%22Segler%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%20A.%22%2C%22lastName%22%3A%22Skinnider%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Allison%20S.%22%2C%22lastName%22%3A%22Walker%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Egon%20L.%22%2C%22lastName%22%3A%22Willighagen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Barbara%22%2C%22lastName%22%3A%22Zdrazil%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nadine%22%2C%22lastName%22%3A%22Ziemert%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rebecca%20J.%20M.%22%2C%22lastName%22%3A%22Goss%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pierre%22%2C%22lastName%22%3A%22Guyomard%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andrea%22%2C%22lastName%22%3A%22Volkamer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hyun%20Uk%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rolf%22%2C%22lastName%22%3A%22M%5Cu00fcller%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%20P.%22%2C%22lastName%22%3A%22Van%20Wezel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gerard%20J.%20P.%22%2C%22lastName%22%3A%22Van%20Westen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anna%20K.%20H.%22%2C%22lastName%22%3A%22Hirsch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Roger%20G.%22%2C%22lastName%22%3A%22Linington%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Serina%20L.%22%2C%22lastName%22%3A%22Robinson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marnix%20H.%22%2C%22lastName%22%3A%22Medema%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2211%5C%2F2023%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41573-023-00774-7%22%2C%22ISSN%22%3A%221474-1776%2C%201474-1784%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41573-023-00774-7%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222023-11-30T19%3A47%3A30Z%22%7D%7D%2C%7B%22key%22%3A%22EEX8QM3A%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Deni%20et%20al.%22%2C%22parsedDate%22%3A%222023%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EDeni%2C%20I.%2C%20Stokes%2C%20B.%20H.%2C%20Ward%2C%20K.%20E.%2C%20Fairhurst%2C%20K.%20J.%2C%20Pasaje%2C%20C.%20F.%20A.%2C%20Yeo%2C%20T.%2C%20Akbar%2C%20S.%2C%20Park%2C%20H.%2C%20Muir%2C%20R.%2C%20Bick%2C%20D.%20S.%2C%20Zhan%2C%20W.%2C%20Zhang%2C%20H.%2C%20Liu%2C%20Y.%20J.%2C%20Ng%2C%20C.%20L.%2C%20Kirkman%2C%20L.%20A.%2C%20Almaliti%2C%20J.%2C%20Gould%2C%20A.%20E.%2C%20Duffey%2C%20M.%2C%20O%26%23x2019%3BDonoghue%2C%20A.%20J.%2C%20%26%23x2026%3B%20Fidock%2C%20D.%20A.%20%282023%29.%20Mitigating%20the%20risk%20of%20antimalarial%20resistance%20via%20covalent%20dual-subunit%20inhibition%20of%20the%20Plasmodium%20proteasome.%20%3Ci%3ECell%20Chemical%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E30%3C%5C%2Fi%3E%285%29%2C%20470-485.e6.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.chembiol.2023.03.002%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.chembiol.2023.03.002%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Mitigating%20the%20risk%20of%20antimalarial%20resistance%20via%20covalent%20dual-subunit%20inhibition%20of%20the%20Plasmodium%20proteasome%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ioanna%22%2C%22lastName%22%3A%22Deni%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Barbara%20H.%22%2C%22lastName%22%3A%22Stokes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kurt%20E.%22%2C%22lastName%22%3A%22Ward%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kate%20J.%22%2C%22lastName%22%3A%22Fairhurst%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Charisse%20Flerida%20A.%22%2C%22lastName%22%3A%22Pasaje%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tomas%22%2C%22lastName%22%3A%22Yeo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shirin%22%2C%22lastName%22%3A%22Akbar%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Heekuk%22%2C%22lastName%22%3A%22Park%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ryan%22%2C%22lastName%22%3A%22Muir%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniella%20S.%22%2C%22lastName%22%3A%22Bick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wenhu%22%2C%22lastName%22%3A%22Zhan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hao%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yi%20Jing%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Caroline%20L.%22%2C%22lastName%22%3A%22Ng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Laura%20A.%22%2C%22lastName%22%3A%22Kirkman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jehad%22%2C%22lastName%22%3A%22Almaliti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexandra%20E.%22%2C%22lastName%22%3A%22Gould%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ma%5Cu00eblle%22%2C%22lastName%22%3A%22Duffey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anthony%20J.%22%2C%22lastName%22%3A%22O%27Donoghue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anne-Catrin%22%2C%22lastName%22%3A%22Uhlemann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jacquin%20C.%22%2C%22lastName%22%3A%22Niles%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paula%20C.A.%22%2C%22lastName%22%3A%22Da%20Fonseca%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gang%22%2C%22lastName%22%3A%22Lin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matthew%22%2C%22lastName%22%3A%22Bogyo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%20A.%22%2C%22lastName%22%3A%22Fidock%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2205%5C%2F2023%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.chembiol.2023.03.002%22%2C%22ISSN%22%3A%2224519456%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS2451945623000612%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222023-09-13T23%3A04%3A09Z%22%7D%7D%2C%7B%22key%22%3A%22KD9JUI8D%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ternon%20et%20al.%22%2C%22parsedDate%22%3A%222022-11-28%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ETernon%2C%20E.%2C%20Thomas%2C%20O.%20P.%2C%20Lem%26%23xE9%3Be%2C%20R.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282022%29.%20Rapid%20Biotic%20and%20Abiotic%20Transformation%20of%20Toxins%20produced%20by%20Ostreopsis.%20cf.%20ovata.%20%3Ci%3EMarine%20Drugs%3C%5C%2Fi%3E%2C%20%3Ci%3E20%3C%5C%2Fi%3E%2812%29%2C%20748.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmd20120748%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmd20120748%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Rapid%20Biotic%20and%20Abiotic%20Transformation%20of%20Toxins%20produced%20by%20Ostreopsis.%20cf.%20ovata%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eva%22%2C%22lastName%22%3A%22Ternon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Olivier%20P.%22%2C%22lastName%22%3A%22Thomas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rodolphe%22%2C%22lastName%22%3A%22Lem%5Cu00e9e%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22The%20dinoflagellate%20Ostreopsis%20cf.%20ovata%20produces%20several%20families%20of%20toxic%20polyketides.%20Despite%20only%20a%20few%20field%20measurements%20of%20these%20phycotoxins%20in%20seawater%20and%20aerosols%2C%20they%20are%20believed%20to%20be%20responsible%20for%20dermatitis%20and%20the%20toxic%20inhalations%20reported%20during%20blooms%20of%20this%20species.%20Therefore%2C%20the%20stability%20of%20these%20compounds%20in%20seawater%20is%20essential%20to%20understanding%20the%20causes%20of%20these%20symptoms%2C%20however%2C%20this%20has%20never%20been%20assessed.%20In%20the%20current%20study%2C%20the%20optimization%20of%20a%20solid%20phase%20extraction%20%28SPE%29%20procedure%20was%20first%20performed%20to%20ensure%20the%20most%20efficient%20extraction%20of%20all%20phycotoxins%20known%20to%20be%20produced%20by%20this%20strain%2C%20including%20the%20recently%20described%20liguriatoxins.%20The%20SPE%20cartridge%20SDBL%5Cu00ae%20under%20non%20acidified%20conditions%20offered%20the%20best%20option.%20The%20stability%20of%20the%20ovatoxins%20and%20the%20liguriatoxins%20under%20biotic%20and%20abiotic%20stress%20was%20assessed%20by%20exposing%20the%20spent%20medium%20of%20a%20culture%20of%20Ostreopsis%20cf.%20ovata%20to%20its%20bacterial%20consortium%20and%20natural%20sunlight.%20A%20rapid%20biotic%20transformation%20was%20detected%20for%20both%20families%20of%20compounds.%20When%20exposed%20to%20bacteria%2C%20the%20half-lives%20of%20the%20ovatoxins%20were%20reached%20before%2010%20h%20and%20at%2036%20h%2C%2097%25%20of%20these%20toxins%20had%20been%20transformed.%20The%20half-lives%20of%20the%20liguriatoxins%20were%2010%20h%20under%20these%20conditions.%20Photolysis%20%28abiotic%20degradation%29%20of%20the%20ovatoxins%20%28T1%5C%2F2%20%3C%2036%20h%29%20was%20faster%20than%20for%20the%20liguriatoxins%20%28T1%5C%2F2%20%3E%2062%20h%29.%20Although%20none%20of%20the%20catabolites%20of%20these%20phycotoxins%20were%20thoroughly%20identified%2C%20an%20untargeted%20metabolomics%20approach%20combined%20with%20molecular%20networking%20highlighted%20the%20presence%20of%20several%20compounds%20exhibiting%20structural%20similarities%20with%20the%20ovatoxins.%20Additional%20work%20should%20confirm%20the%20preliminary%20findings%20on%20these%20potential%20ovatoxins%5Cu2019%20catabolites%20and%20their%20biological%20properties.%20The%20rapid%20transformation%20of%20O.%20cf.%20ovata%5Cu2019s%20phycotoxins%20introduces%20questions%20concerning%20their%20presence%20in%20seawater%20and%20their%20dispersion%20in%20the%20sea%20spray%20aerosols.%20The%20compounds%20involved%20in%20the%20toxic%20inhalations%20and%20dermatitis%20often%20experienced%20by%20beachgoers%20may%20stem%20from%20the%20catabolites%20of%20these%20toxins%20or%20even%20unrelated%20and%20as%20yet%20unidentified%20compounds.%22%2C%22date%22%3A%222022-11-28%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.3390%5C%2Fmd20120748%22%2C%22ISSN%22%3A%221660-3397%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.mdpi.com%5C%2F1660-3397%5C%2F20%5C%2F12%5C%2F748%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222023-01-26T00%3A13%3A27Z%22%7D%7D%2C%7B%22key%22%3A%22JJNDPAUK%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Le%5Cu00e3o%20et%20al.%22%2C%22parsedDate%22%3A%222022-11-01%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELe%26%23xE3%3Bo%2C%20T.%20F.%2C%20Wang%2C%20M.%2C%20da%26%23xA0%3BSilva%2C%20R.%2C%20Gurevich%2C%20A.%2C%20Bauermeister%2C%20A.%2C%20Gomes%2C%20P.%20W.%20P.%2C%20Brejnrod%2C%20A.%2C%20Glukhov%2C%20E.%2C%20Aron%2C%20A.%20T.%2C%20Louwen%2C%20J.%20J.%20R.%2C%20Kim%2C%20H.%20W.%2C%20Reher%2C%20R.%2C%20Fiore%2C%20M.%20F.%2C%20van%26%23xA0%3Bder%26%23xA0%3BHooft%2C%20J.%20J.%20J.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20L.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20Bandeira%2C%20N.%2C%20%26amp%3B%20Dorrestein%2C%20P.%20C.%20%282022%29.%20NPOmix%3A%20A%20machine%20learning%20classifier%20to%20connect%20mass%20spectrometry%20fragmentation%20data%20to%20biosynthetic%20gene%20clusters.%20%3Ci%3EPNAS%20Nexus%3C%5C%2Fi%3E%2C%20%3Ci%3E1%3C%5C%2Fi%3E%285%29%2C%20pgac257.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fpnasnexus%5C%2Fpgac257%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fpnasnexus%5C%2Fpgac257%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22NPOmix%3A%20A%20machine%20learning%20classifier%20to%20connect%20mass%20spectrometry%20fragmentation%20data%20to%20biosynthetic%20gene%20clusters%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tiago%20F%22%2C%22lastName%22%3A%22Le%5Cu00e3o%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mingxun%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ricardo%22%2C%22lastName%22%3A%22da%5Cu00a0Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexey%22%2C%22lastName%22%3A%22Gurevich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anelize%22%2C%22lastName%22%3A%22Bauermeister%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paulo%20Wender%20P%22%2C%22lastName%22%3A%22Gomes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Asker%22%2C%22lastName%22%3A%22Brejnrod%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Evgenia%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Allegra%20T%22%2C%22lastName%22%3A%22Aron%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Joris%20J%20R%22%2C%22lastName%22%3A%22Louwen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hyun%20Woo%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raphael%22%2C%22lastName%22%3A%22Reher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marli%20F%22%2C%22lastName%22%3A%22Fiore%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Justin%20J%20J%22%2C%22lastName%22%3A%22van%5Cu00a0der%5Cu00a0Hooft%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lena%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nuno%22%2C%22lastName%22%3A%22Bandeira%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pieter%20C%22%2C%22lastName%22%3A%22Dorrestein%22%7D%2C%7B%22creatorType%22%3A%22editor%22%2C%22firstName%22%3A%22Amalio%22%2C%22lastName%22%3A%22Telenti%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Microbial%20specialized%20metabolites%20are%20an%20important%20source%20of%20and%20inspiration%20for%20many%20pharmaceuticals%2C%20biotechnological%20products%20and%20play%20key%20roles%20in%20ecological%20processes.%20Untargeted%20metabolomics%20using%20liquid%20chromatography%20coupled%20with%20tandem%20mass%20spectrometry%20is%20an%20efficient%20technique%20to%20access%20metabolites%20from%20fractions%20and%20even%20environmental%20crude%20extracts.%20Nevertheless%2C%20metabolomics%20is%20limited%20in%20predicting%20structures%20or%20bioactivities%20for%20cryptic%20metabolites.%20Efficiently%20linking%20the%20biosynthetic%20potential%20inferred%20from%20%28meta%29genomics%20to%20the%20specialized%20metabolome%20would%20accelerate%20drug%20discovery%20programs%20by%20allowing%20metabolomics%20to%20make%20use%20of%20genetic%20predictions.%20Here%2C%20we%20present%20a%20k-nearest%20neighbor%20classifier%20to%20systematically%20connect%20mass%20spectrometry%20fragmentation%20spectra%20to%20their%20corresponding%20biosynthetic%20gene%20clusters%20%28independent%20of%20their%20chemical%20class%29.%20Our%20new%20pattern-based%20genome%20mining%20pipeline%20links%20biosynthetic%20genes%20to%20metabolites%20that%20they%20encode%20for%2C%20as%20detected%20via%20mass%20spectrometry%20from%20bacterial%20cultures%20or%20environmental%20microbiomes.%20Using%20paired%20datasets%20that%20include%20validated%20genes-mass%20spectral%20links%20from%20the%20Paired%20Omics%20Data%20Platform%2C%20we%20demonstrate%20this%20approach%20by%20automatically%20linking%2018%20previously%20known%20mass%20spectra%20%2817%20for%20which%20the%20biosynthesis%20gene%20clusters%20can%20be%20found%20at%20the%20MIBiG%20database%20plus%20palmyramide%20A%29%20to%20their%20corresponding%20previously%20experimentally%20validated%20biosynthetic%20genes%20%28e.g.%2C%20via%20nuclear%20magnetic%20resonance%20or%20genetic%20engineering%29.%20We%20illustrated%20a%20computational%20example%20of%20how%20to%20use%20our%20Natural%20Products%20Mixed%20Omics%20%28NPOmix%29%20tool%20for%20siderophore%20mining%20that%20can%20be%20reproduced%20by%20the%20users.%20We%20conclude%20that%20NPOmix%20minimizes%20the%20need%20for%20culturing%20%28it%20worked%20well%20on%20microbiomes%29%20and%20facilitates%20specialized%20metabolite%20prioritization%20based%20on%20integrative%20omics%20mining.%22%2C%22date%22%3A%222022-11-01%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1093%5C%2Fpnasnexus%5C%2Fpgac257%22%2C%22ISSN%22%3A%222752-6542%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fpnasnexus%5C%2Farticle%5C%2Fdoi%5C%2F10.1093%5C%2Fpnasnexus%5C%2Fpgac257%5C%2F6847575%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%2C%22X8P588WG%22%5D%2C%22dateModified%22%3A%222023-10-25T17%3A00%3A04Z%22%7D%7D%2C%7B%22key%22%3A%22PSFTKD7I%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Reher%20et%20al.%22%2C%22parsedDate%22%3A%222022-08-08%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EReher%2C%20R.%2C%20Aron%2C%20A.%20T.%2C%20Fajtov%26%23xE1%3B%2C%20P.%2C%20Stincone%2C%20P.%2C%20Wagner%2C%20B.%2C%20P%26%23xE9%3Brez-Lorente%2C%20A.%20I.%2C%20Liu%2C%20C.%2C%20Shalom%2C%20I.%20Y.%20B.%2C%20Bittremieux%2C%20W.%2C%20Wang%2C%20M.%2C%20Jeong%2C%20K.%2C%20Matos-Hernandez%2C%20M.%20L.%2C%20Alexander%2C%20K.%20L.%2C%20Caro-Diaz%2C%20E.%20J.%2C%20Naman%2C%20C.%20B.%2C%20Scanlan%2C%20J.%20H.%20W.%2C%20Hochban%2C%20P.%20M.%20M.%2C%20Diederich%2C%20W.%20E.%2C%20Molina-Santiago%2C%20C.%2C%20%26%23x2026%3B%20Petras%2C%20D.%20%282022%29.%20Native%20metabolomics%20identifies%20the%20rivulariapeptolide%20family%20of%20protease%20inhibitors.%20%3Ci%3ENature%20Communications%3C%5C%2Fi%3E%2C%20%3Ci%3E13%3C%5C%2Fi%3E%281%29%2C%204619.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-022-32016-6%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-022-32016-6%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Native%20metabolomics%20identifies%20the%20rivulariapeptolide%20family%20of%20protease%20inhibitors%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raphael%22%2C%22lastName%22%3A%22Reher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Allegra%20T.%22%2C%22lastName%22%3A%22Aron%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pavla%22%2C%22lastName%22%3A%22Fajtov%5Cu00e1%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paolo%22%2C%22lastName%22%3A%22Stincone%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Berenike%22%2C%22lastName%22%3A%22Wagner%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alicia%20I.%22%2C%22lastName%22%3A%22P%5Cu00e9rez-Lorente%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chenxi%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ido%20Y.%20Ben%22%2C%22lastName%22%3A%22Shalom%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wout%22%2C%22lastName%22%3A%22Bittremieux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mingxun%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kyowon%22%2C%22lastName%22%3A%22Jeong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marie%20L.%22%2C%22lastName%22%3A%22Matos-Hernandez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kelsey%20L.%22%2C%22lastName%22%3A%22Alexander%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eduardo%20J.%22%2C%22lastName%22%3A%22Caro-Diaz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20Benjamin%22%2C%22lastName%22%3A%22Naman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20H.%20William%22%2C%22lastName%22%3A%22Scanlan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Phil%20M.%20M.%22%2C%22lastName%22%3A%22Hochban%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wibke%20E.%22%2C%22lastName%22%3A%22Diederich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carlos%22%2C%22lastName%22%3A%22Molina-Santiago%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Diego%22%2C%22lastName%22%3A%22Romero%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Khaled%20A.%22%2C%22lastName%22%3A%22Selim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Peter%22%2C%22lastName%22%3A%22Sass%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Heike%22%2C%22lastName%22%3A%22Br%5Cu00f6tz-Oesterhelt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chambers%20C.%22%2C%22lastName%22%3A%22Hughes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pieter%20C.%22%2C%22lastName%22%3A%22Dorrestein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anthony%20J.%22%2C%22lastName%22%3A%22O%5Cu2019Donoghue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniel%22%2C%22lastName%22%3A%22Petras%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%5Cn%20%20%20%20%20%20%20%20%20%20%20%20The%20identity%20and%20biological%20activity%20of%20most%20metabolites%20still%20remain%20unknown.%20A%20bottleneck%20in%20the%20exploration%20of%20metabolite%20structures%20and%20pharmaceutical%20activities%20is%20the%20compound%20purification%20needed%20for%20bioactivity%20assignments%20and%20downstream%20structure%20elucidation.%20To%20enable%20bioactivity-focused%20compound%20identification%20from%20complex%20mixtures%2C%20we%20develop%20a%20scalable%20native%20metabolomics%20approach%20that%20integrates%20non-targeted%20liquid%20chromatography%20tandem%20mass%20spectrometry%20and%20detection%20of%20protein%20binding%20via%20native%20mass%20spectrometry.%20A%20native%20metabolomics%20screen%20for%20protease%20inhibitors%20from%20an%20environmental%20cyanobacteria%20community%20reveals%2030%20chymotrypsin-binding%20cyclodepsipeptides.%20Guided%20by%20the%20native%20metabolomics%20results%2C%20we%20select%20and%20purify%20five%20of%20these%20compounds%20for%20full%20structure%20elucidation%20via%20tandem%20mass%20spectrometry%2C%20chemical%20derivatization%2C%20and%20nuclear%20magnetic%20resonance%20spectroscopy%20as%20well%20as%20evaluation%20of%20their%20biological%20activities.%20These%20results%20identify%20rivulariapeptolides%20as%20a%20family%20of%20serine%20protease%20inhibitors%20with%20nanomolar%20potency%2C%20highlighting%20native%20metabolomics%20as%20a%5Cu00a0promising%20approach%20for%20drug%20discovery%2C%20chemical%20ecology%2C%20and%20chemical%20biology%20studies.%22%2C%22date%22%3A%222022-08-08%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41467-022-32016-6%22%2C%22ISSN%22%3A%222041-1723%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41467-022-32016-6%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-08-31T22%3A04%3A21Z%22%7D%7D%2C%7B%22key%22%3A%22V3SJ6QLZ%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Phan%20et%20al.%22%2C%22parsedDate%22%3A%222022-07-26%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EPhan%2C%20V.%20V.%2C%20Mosier%2C%20C.%2C%20Yoon%2C%20M.%20C.%2C%20Glukhov%2C%20E.%2C%20Caffrey%2C%20C.%20R.%2C%20O%26%23x2019%3BDonoghue%2C%20A.%20J.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Hook%2C%20V.%20%282022%29.%20Discovery%20of%20pH-Selective%20Marine%20and%20Plant%20Natural%20Product%20Inhibitors%20of%20Cathepsin%20B%20Revealed%20by%20Screening%20at%20Acidic%20and%20Neutral%20pH%20Conditions.%20%3Ci%3EACS%20Omega%3C%5C%2Fi%3E%2C%20%3Ci%3E7%3C%5C%2Fi%3E%2829%29%2C%2025346%26%23x2013%3B25352.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facsomega.2c02287%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facsomega.2c02287%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Discovery%20of%20pH-Selective%20Marine%20and%20Plant%20Natural%20Product%20Inhibitors%20of%20Cathepsin%20B%20Revealed%20by%20Screening%20at%20Acidic%20and%20Neutral%20pH%20Conditions%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Von%20V.%22%2C%22lastName%22%3A%22Phan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Charles%22%2C%22lastName%22%3A%22Mosier%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%20C.%22%2C%22lastName%22%3A%22Yoon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Evgenia%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Conor%20R.%22%2C%22lastName%22%3A%22Caffrey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anthony%20J.%22%2C%22lastName%22%3A%22O%5Cu2019Donoghue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vivian%22%2C%22lastName%22%3A%22Hook%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222022-07-26%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1021%5C%2Facsomega.2c02287%22%2C%22ISSN%22%3A%222470-1343%2C%202470-1343%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fpubs.acs.org%5C%2Fdoi%5C%2F10.1021%5C%2Facsomega.2c02287%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-08-15T17%3A18%3A32Z%22%7D%7D%2C%7B%22key%22%3A%22QNPV95T9%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Taton%20et%20al.%22%2C%22parsedDate%22%3A%222022-07-15%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ETaton%2C%20A.%2C%20Rohrer%2C%20S.%2C%20Diaz%2C%20B.%2C%20Reher%2C%20R.%2C%20Caraballo%20Rodriguez%2C%20A.%20M.%2C%20Pierce%2C%20M.%20L.%2C%20Dorrestein%2C%20P.%20C.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20L.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Golden%2C%20J.%20W.%20%282022%29.%20Heterologous%20Expression%20in%20%3Ci%3EAnabaena%3C%5C%2Fi%3E%20of%20the%20Columbamide%20Pathway%20from%20the%20Cyanobacterium%20%3Ci%3EMoorena%20bouillonii%3C%5C%2Fi%3E%20and%20Production%20of%20New%20Analogs.%20%3Ci%3EACS%20Chemical%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E17%3C%5C%2Fi%3E%287%29%2C%201910%26%23x2013%3B1923.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facschembio.2c00347%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facschembio.2c00347%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Heterologous%20Expression%20in%20%3Ci%3EAnabaena%3C%5C%2Fi%3E%20of%20the%20Columbamide%20Pathway%20from%20the%20Cyanobacterium%20%3Ci%3EMoorena%20bouillonii%3C%5C%2Fi%3E%20and%20Production%20of%20New%20Analogs%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Arnaud%22%2C%22lastName%22%3A%22Taton%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sebastian%22%2C%22lastName%22%3A%22Rohrer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Brienna%22%2C%22lastName%22%3A%22Diaz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raphael%22%2C%22lastName%22%3A%22Reher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andres%20Mauricio%22%2C%22lastName%22%3A%22Caraballo%20Rodriguez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marsha%20L.%22%2C%22lastName%22%3A%22Pierce%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pieter%20C.%22%2C%22lastName%22%3A%22Dorrestein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lena%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20W.%22%2C%22lastName%22%3A%22Golden%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222022-07-15%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1021%5C%2Facschembio.2c00347%22%2C%22ISSN%22%3A%221554-8929%2C%201554-8937%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fpubs.acs.org%5C%2Fdoi%5C%2F10.1021%5C%2Facschembio.2c00347%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%2C%22X8P588WG%22%5D%2C%22dateModified%22%3A%222022-07-27T18%3A47%3A42Z%22%7D%7D%2C%7B%22key%22%3A%22YSSSHJE4%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22He%20et%20al.%22%2C%22parsedDate%22%3A%222022-07-13%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EHe%2C%20Y.%2C%20Suyama%2C%20T.%20L.%2C%20Kim%2C%20H.%2C%20Glukhov%2C%20E.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282022%29.%20Discovery%20of%20Novel%20Tyrosinase%20Inhibitors%20From%20Marine%20Cyanobacteria.%20%3Ci%3EFrontiers%20in%20Microbiology%3C%5C%2Fi%3E%2C%20%3Ci%3E13%3C%5C%2Fi%3E%2C%20912621.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3389%5C%2Ffmicb.2022.912621%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3389%5C%2Ffmicb.2022.912621%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Discovery%20of%20Novel%20Tyrosinase%20Inhibitors%20From%20Marine%20Cyanobacteria%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yifan%22%2C%22lastName%22%3A%22He%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Takashi%20L.%22%2C%22lastName%22%3A%22Suyama%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hyunwoo%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Evgenia%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22Tyrosinase%2C%20an%20important%20oxidase%20involved%20in%20the%20primary%20immune%20response%20in%20humans%2C%20can%20sometimes%20become%20problematic%20as%20it%20can%20catalyze%20undesirable%20oxidation%20reactions.%20Therefore%2C%20for%20decades%20there%20has%20been%20a%20strong%20pharmaceutical%20interest%20in%20the%20discovery%20of%20novel%20inhibitors%20of%20this%20enzyme.%20Recent%20studies%20have%20also%20indicated%20that%20tyrosinase%20inhibitors%20can%20potentially%20be%20used%20in%20the%20treatment%20of%20melanoma%20cancer.%20Over%20the%20years%2C%20many%20new%20tyrosinase%20inhibitors%20have%20been%20discovered%20from%20various%20natural%20sources%3B%20however%2C%20marine%20natural%20products%20%28MNPs%29%20have%20contributed%20only%20a%20small%20number%20of%20promising%20candidates.%20Therefore%2C%20in%20this%20study%20we%20focused%20on%20the%20discovery%20of%20new%20MNP%20tyrosinase%20inhibitors%20of%20marine%20cyanobacterial%20and%20algal%20origins.%20A%20colorimetric%20tyrosinase%20inhibitory%20assay%20was%20used%20to%20screen%20over%204%2C500%20marine%20extracts%20against%20mushroom%20tyrosinase%20%28%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20A.%20bisporus%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%29.%20Our%20results%20revealed%20that%20scytonemin%20monomer%20%28ScyM%29%2C%20a%20pure%20compound%20from%20our%20compound%20library%20and%20also%20the%20monomeric%20last-step%20precursor%20in%20the%20biosynthesis%20of%20the%20well-known%20cyanobacterial%20sunscreen%20pigment%20%5Cu201cscytonemin%2C%5Cu201d%20consistently%20showed%20the%20highest%20tyrosinase%20inhibitory%20score.%20Determination%20of%20the%20half%20maximal%20inhibitory%20concentration%20%28IC%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%2050%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%29%20further%20indicated%20that%20ScyM%20is%20more%20potent%20than%20the%20commonly%20used%20commercial%20inhibitor%20standard%20%5Cu201ckojic%20acid%5Cu201d%20%28KA%3B%20IC%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%2050%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20of%20ScyM%3A%204.90%5Cu2009%5Cu03bcM%20vs.%20IC%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%2050%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20of%20KA%3A%2011.31%5Cu2009%5Cu03bcM%29.%20After%20a%20scaled-up%20chemical%20synthesis%20of%20ScyM%20as%20well%20as%20its%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20O%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20-methyl%20analog%20%28ScyM-OMe%29%2C%20we%20conducted%20a%20series%20of%20follow-up%20studies%20on%20their%20structures%2C%20inhibitory%20properties%2C%20and%20mode%20of%20inhibition.%20Our%20results%20supported%20ScyM%20as%20the%20second%20case%20ever%20of%20a%20novel%20tyrosinase%20inhibitory%20compound%20based%20on%20a%20marine%20cyanobacterial%20natural%20product.%20The%20excellent%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20in%20vitro%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20performance%20of%20ScyM%20makes%20it%20a%20promising%20candidate%20for%20applications%20such%20as%20a%20skin-whitening%20agent%20or%20an%20adjuvant%20therapy%20for%20melanoma%20cancer%20treatment.%22%2C%22date%22%3A%222022-7-13%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3389%5C%2Ffmicb.2022.912621%22%2C%22ISSN%22%3A%221664-302X%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.frontiersin.org%5C%2Farticles%5C%2F10.3389%5C%2Ffmicb.2022.912621%5C%2Ffull%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-08-30T15%3A23%3A35Z%22%7D%7D%2C%7B%22key%22%3A%22Y2DZDBE2%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Li%20et%20al.%22%2C%22parsedDate%22%3A%222022-07-04%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELi%2C%20F.-L.%2C%20Fu%2C%20V.%2C%20Liu%2C%20G.%2C%20Tang%2C%20T.%2C%20Konradi%2C%20A.%20W.%2C%20Peng%2C%20X.%2C%20Kemper%2C%20E.%2C%20Cravatt%2C%20B.%20F.%2C%20Franklin%2C%20J.%20M.%2C%20Wu%2C%20Z.%2C%20Mayfield%2C%20J.%2C%20Dixon%2C%20J.%20E.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Guan%2C%20K.-L.%20%282022%29.%20Hippo%20pathway%20regulation%20by%20phosphatidylinositol%20transfer%20protein%20and%20phosphoinositides.%20%3Ci%3ENature%20Chemical%20Biology%3C%5C%2Fi%3E.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41589-022-01061-z%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41589-022-01061-z%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Hippo%20pathway%20regulation%20by%20phosphatidylinositol%20transfer%20protein%20and%20phosphoinositides%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fu-Long%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vivian%22%2C%22lastName%22%3A%22Fu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Guangbo%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tracy%22%2C%22lastName%22%3A%22Tang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andrei%20W.%22%2C%22lastName%22%3A%22Konradi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiao%22%2C%22lastName%22%3A%22Peng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Esther%22%2C%22lastName%22%3A%22Kemper%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Benjamin%20F.%22%2C%22lastName%22%3A%22Cravatt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20Matthew%22%2C%22lastName%22%3A%22Franklin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhengming%22%2C%22lastName%22%3A%22Wu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Joshua%22%2C%22lastName%22%3A%22Mayfield%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jack%20E.%22%2C%22lastName%22%3A%22Dixon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kun-Liang%22%2C%22lastName%22%3A%22Guan%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222022-07-04%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41589-022-01061-z%22%2C%22ISSN%22%3A%221552-4450%2C%201552-4469%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41589-022-01061-z%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-27T18%3A49%3A37Z%22%7D%7D%2C%7B%22key%22%3A%22JWGXBIH5%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Wang%20et%20al.%22%2C%22parsedDate%22%3A%222022-04%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EWang%2C%20Y.%2C%20Glukhov%2C%20E.%2C%20He%2C%20Y.%20F.%2C%20Liu%2C%20Y.%20Y.%2C%20Zhou%2C%20L.%20J.%2C%20Ma%2C%20X.%20X.%2C%20Hu%2C%20X.%20Q.%2C%20Hong%2C%20P.%20Z.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Zhang%2C%20Y.%20%282022%29.%20Secondary%20metabolite%20variation%20and%20bioactivities%20of%20two%20marine%20aspergillus%20strains%20in%20static%20co-culture%20investigated%20by%20molecular%20network%20analysis%20and%20multiple%20database%20mining%20based%20on%20LC-PDA-MS%5C%2FMS.%20%3Ci%3EAntibiotics-Basel%3C%5C%2Fi%3E%2C%20%3Ci%3E11%3C%5C%2Fi%3E%284%29%2C%2026.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fantibiotics11040513%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fantibiotics11040513%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Secondary%20metabolite%20variation%20and%20bioactivities%20of%20two%20marine%20aspergillus%20strains%20in%20static%20co-culture%20investigated%20by%20molecular%20network%20analysis%20and%20multiple%20database%20mining%20based%20on%20LC-PDA-MS%5C%2FMS%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%20F.%22%2C%22lastName%22%3A%22He%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%20Y.%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%20J.%22%2C%22lastName%22%3A%22Zhou%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22X.%20X.%22%2C%22lastName%22%3A%22Ma%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22X.%20Q.%22%2C%22lastName%22%3A%22Hu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%20Z.%22%2C%22lastName%22%3A%22Hong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Zhang%22%7D%5D%2C%22abstractNote%22%3A%22Co-culture%20is%20known%20as%20an%20efficient%20way%20to%20explore%20the%20metabolic%20potential%20of%20fungal%20strains%20for%20new%20antibiotics%20and%20other%20therapeutic%20agents%20that%20could%20counter%20emerging%20health%20issues.%20To%20study%20the%20effect%20of%20co-culture%20on%20the%20secondary%20metabolites%20and%20bioactivities%20of%20two%20marine%20strains%2C%20Aspergillus%20terreus%20C23-3%20and%20Aspergillus.%20unguis%20DLEP2008001%2C%20they%20were%20co-cultured%20in%20live%20or%20inactivated%20forms%20successively%20or%20simultaneously.%20The%20mycelial%20morphology%20and%20high-performance%20thin%20layer%20chromatography%20%28HPTLC%29%20including%20bioautography%20of%20the%20fermentation%20extracts%20were%20recorded.%20Furthermore%2C%20the%20agar%20cup-plate%20method%20was%20used%20to%20compare%20the%20antimicrobial%20activity%20of%20the%20extracts.%20Based%20on%20the%20above%2C%20liquid%20chromatography-photodiode%20array-tandem%20mass%20spectrometry%20%28LC-PDA-MS%5C%2FMS%29%20together%20with%20Global%20Natural%20Products%20Social%20molecular%20networking%20%28GNPS%29%20and%20multiple%20natural%20products%20database%20mining%20were%20used%20to%20further%20analyze%20their%20secondary%20metabolite%20variations.%20The%20comprehensive%20results%20showed%20the%20following%20trends%3A%20%281%29%20The%20strain%20first%20inoculated%20will%20strongly%20inhibit%20the%20growth%20and%20metabolism%20of%20the%20latter%20inoculated%20one%3B%20%282%29%20Autoclaved%20A.%20unguis%20exerted%20a%20strong%20inducing%20effect%20on%20later%20inoculated%20A.%20terreus%2C%20while%20the%20autoclaved%20A.%20terreus%20showed%20high%20stability%20of%20its%20metabolites%20and%20still%20potently%20suppressed%20the%20growth%20and%20metabolism%20of%20A.%20unguis%3B%20%283%29%20When%20the%20two%20strains%20are%20inoculated%20simultaneously%2C%20they%20both%20grow%20and%20produce%20metabolites%3B%20however%2C%20the%20A.%20terreus%20seemed%20to%20be%20more%20strongly%20induced%20by%20live%20A.%20unguis%20and%20this%20inducing%20effect%20surpassed%20that%20of%20the%20autoclaved%20A.%20unguis.%20Under%20some%20of%20the%20conditions%2C%20the%20extracts%20showed%20higher%20antimicrobial%20activity%20than%20the%20axenic%20cultures.%20Totally%2C%20A.%20unguis%20was%20negative%20in%20response%20but%20potent%20in%20stimulating%20its%20rival%20while%20A.%20terreus%20had%20the%20opposite%20effect.%20Fifteen%20MS%20detectable%20and%5C%2For%20UV%20active%20peaks%20showed%20different%20yields%20in%20co-cultures%20vs.%20the%20corresponding%20axenic%20culture.%20GNPS%20analysis%20assisted%20by%20multiple%20natural%20products%20databases%20mining%20%28PubChem%2C%20Dictionary%20of%20Natural%20Products%2C%20NPASS%2C%20etc.%29%20gave%20reasonable%20annotations%20for%20some%20of%20these%20peaks%2C%20including%20antimicrobial%20compounds%20such%20as%20unguisin%20A%2C%20lovastatin%2C%20and%20nidulin.%20However%2C%20some%20of%20the%20peaks%20were%20correlated%20with%20antagonistic%20properties%20and%20remain%20as%20possible%20novel%20compounds%20without%20mass%20or%20UV%20matching%20hits%20from%20any%20database.%20It%20is%20intriguing%20that%20the%20two%20strains%20both%20synthesize%20chemical%20%27weapons%27%20for%20antagonism%2C%20and%20that%20these%20are%20upregulated%20when%20needed%20in%20competitive%20co-culture%20environment.%20At%20the%20same%20time%2C%20compounds%20not%20useful%20in%20this%20antagonistic%20setting%20are%20downregulated%20in%20their%20expression.%20Some%20of%20the%20natural%20products%20produced%20during%20antagonism%20are%20unknown%20chlorinated%20metabolites%20and%20deserve%20further%20study%20for%20their%20antimicrobial%20properties.%20In%20summary%2C%20this%20study%20disclosed%20the%20different%20responses%20of%20two%20Aspergillus%20strains%20in%20co-culture%2C%20revealed%20their%20metabolic%20variation%2C%20and%20displayed%20new%20opportunities%20for%20antibiotic%20discovery.%22%2C%22date%22%3A%222022%5C%2F04%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.3390%5C%2Fantibiotics11040513%22%2C%22ISSN%22%3A%222079-6382%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A43Z%22%7D%7D%2C%7B%22key%22%3A%22LF2X9MIM%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Da%20Silva%20et%20al.%22%2C%22parsedDate%22%3A%222022-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EDa%20Silva%2C%20E.%20B.%2C%20Sharma%2C%20V.%2C%20Hernandez-Alvarez%2C%20L.%2C%20Tang%2C%20A.%20H.%2C%20Stoye%2C%20A.%2C%20O%26%23x2019%3BDonoghue%2C%20A.%20J.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20Payne%2C%20R.%20J.%2C%20McKerrow%2C%20J.%20H.%2C%20%26amp%3B%20Podust%2C%20L.%20M.%20%282022%29.%20Intramolecular%20interactions%20enhance%20the%20potency%20of%20gallinamide%20A%20analogues%20against%20Trypanosoma%20cruzi.%20%3Ci%3EJournal%20of%20Medicinal%20Chemistry%3C%5C%2Fi%3E%2C%20%3Ci%3E65%3C%5C%2Fi%3E%285%29%2C%204255%26%23x2013%3B4269.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jmedchem.1c02063%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jmedchem.1c02063%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Intramolecular%20interactions%20enhance%20the%20potency%20of%20gallinamide%20A%20analogues%20against%20Trypanosoma%20cruzi%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%20B.%22%2C%22lastName%22%3A%22Da%20Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22V.%22%2C%22lastName%22%3A%22Sharma%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Hernandez-Alvarez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20H.%22%2C%22lastName%22%3A%22Tang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Stoye%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22O%27Donoghue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%20J.%22%2C%22lastName%22%3A%22Payne%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20H.%22%2C%22lastName%22%3A%22McKerrow%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%20M.%22%2C%22lastName%22%3A%22Podust%22%7D%5D%2C%22abstractNote%22%3A%22Gallinamide%20A%2C%20a%20metabolite%20of%20the%20marine%20cyanobacterium%20Schizothrix%20sp.%2C%20selectively%20inhibits%20cathepsin%20L-like%20cysteine%20proteases.%20We%20evaluated%20the%20potency%20of%20gallinamide%20A%20and%2023%20synthetic%20analogues%20against%20intracellular%20Trypanosoma%20cruzi%20amastigotes%20and%20the%20cysteine%20protease%2C%20cruzain.%20We%20determined%20the%20co-crystal%20structures%20of%20cruzain%20with%20gallinamide%20A%20and%20two%20synthetic%20analogues%20at%20similar%20to%202%20angstrom%20angstrom.%20SAR%20data%20revealed%20that%20the%20N-terminal%20end%20of%20gallinamide%20A%20is%20loosely%20bound%20and%20weakly%20contributes%20in%20drug-target%20interactions.%20At%20the%20C-terminus%2C%20the%20intramolecular%20pi-pi%20stacking%20interactions%20between%20the%20aromatic%20substituents%20at%20P1%27%20and%20P1%20restrict%20the%20bioactive%20conformation%20of%20the%20inhibitors%2C%20thus%20minimizing%20the%20entropic%20loss%20associated%20with%20target%20binding.%20Molecular%20dynamics%20simulations%20showed%20that%20in%20the%20absence%20of%20an%20aromatic%20group%20at%20P1%2C%20the%20substituent%20at%20P1%27%20interacts%20with%20tryptophan-184.%20The%20P1-P1%27%20interactions%20had%20no%20effect%20on%20anti-cruzain%20activity%2C%20whereas%20anti-T.%20cruzi%20potency%20increased%20by%20similar%20to%20fivefold%2C%20likely%20due%20to%20an%20increase%20in%20solubility%5C%2Fpermeability%20of%20the%20analogues.%22%2C%22date%22%3A%222022%5C%2F03%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.jmedchem.1c02063%22%2C%22ISSN%22%3A%220022-2623%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A35Z%22%7D%7D%2C%7B%22key%22%3A%22C4B8ENEL%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Mehrotra%20et%20al.%22%2C%22parsedDate%22%3A%222022-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EMehrotra%2C%20S.%2C%20Pierce%2C%20M.%20L.%2C%20Cao%2C%20Z.%20Y.%2C%20Jabba%2C%20S.%20V.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Murray%2C%20T.%20F.%20%282022%29.%20Antillatoxin-stimulated%20neurite%20outgrowth%20involves%20the%20brain-derived%20neurotrophic%20factor%20%28BDNF%29-tropomyosin%20related%20kinase%20B%20%28TrkB%29%20aignaling%20pathway%20br.%20%3Ci%3EJournal%20of%20Natural%20Products%3C%5C%2Fi%3E%2C%20%3Ci%3E85%3C%5C%2Fi%3E%283%29%2C%20562%26%23x2013%3B571.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.1c01001%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.1c01001%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Antillatoxin-stimulated%20neurite%20outgrowth%20involves%20the%20brain-derived%20neurotrophic%20factor%20%28BDNF%29-tropomyosin%20related%20kinase%20B%20%28TrkB%29%20aignaling%20pathway%20br%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Mehrotra%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20L.%22%2C%22lastName%22%3A%22Pierce%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Z.%20Y.%22%2C%22lastName%22%3A%22Cao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%20V.%22%2C%22lastName%22%3A%22Jabba%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%20F.%22%2C%22lastName%22%3A%22Murray%22%7D%5D%2C%22abstractNote%22%3A%22Voltage-gated%20sodium%20channel%20%28VGSC%29%20activators%20promote%20neurite%20outgrowth%20byaugmenting%20intracellular%20Na%2Bconcentration%20%28%5BNa%2B%5Di%29%20and%20upregulating%20N-methyl-D-aspartate%20receptor%28NMDAR%29%20function.%20NMDAR%20activation%20stimulates%20calcium%20%28Ca2%2B%29influx%20and%20increases%20brain-derivedneurotrophic%20factor%20%28BDNF%29%20release%20and%20activation%20of%20tropomyosin%20receptor%20kinase%20B%20%28TrkB%29signaling.%20The%20BDNF-TrkB%20pathway%20has%20been%20implicated%20in%20activity-dependent%20neuronaldevelopment.%20We%20have%20previously%20shown%20that%20antillatoxin%20%28ATX%29%2C%20a%20novel%20lipopeptide%20isolatedfrom%20the%20cyanobacteriumMoorea%20producens%2C%20is%20a%20VGSC%20activator%20that%20produces%20an%20elevation%20of%20%5BNa%2B%5Di.Here%20we%20address%20the%20effect%20of%20ATX%20on%20the%20synthesis%20and%20release%20of%20BDNF%20and%20determine%20the%20signalingmechanisms%20by%20which%20ATX%20enhances%20neurite%20outgrowth%20in%20immature%20cerebrocortical%20neurons.%20ATXtreatment%20produced%20a%20concentration-dependent%20release%20of%20BDNF.%20Acute%20treatment%20with%20ATX%20alsoresulted%20in%20increased%20synthesis%20of%20BDNF.%20ATX%20stimulation%20of%20neurite%20outgrowth%20was%20prevented%20bypretreatment%20with%20a%20TrkB%20inhibitor%20or%20transfection%20with%20a%20dominant-negative%20Trk-B.%20The%20ATXactivation%20of%20TrkB%20and%20Akt%20was%20blocked%20by%20both%20a%20NMDAR%20antagonist%20%28MK-801%29%20and%20a%20VGSCblocker%20%28tetrodotoxin%29.%20These%20results%20suggest%20that%20VGSC%20activators%20such%20as%20the%20structurally%20novelATX%20may%20represent%20a%20new%20pharmacological%20strategy%20to%20promote%20neuronal%20plasticity%20through%20a%20NMDAR-BDNF-TrkB-dependent%20mechanism%22%2C%22date%22%3A%222022%5C%2F03%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.jnatprod.1c01001%22%2C%22ISSN%22%3A%220163-3864%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A23Z%22%7D%7D%2C%7B%22key%22%3A%22JU9E7V75%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ashhurst%20et%20al.%22%2C%22parsedDate%22%3A%222022-02%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EAshhurst%2C%20A.%20S.%2C%20Tang%2C%20A.%20H.%2C%20Fajtova%2C%20P.%2C%20Yoon%2C%20M.%20C.%2C%20Aggarwal%2C%20A.%2C%20Bedding%2C%20M.%20J.%2C%20Stoye%2C%20A.%2C%20Beretta%2C%20L.%2C%20Pwee%2C%20D.%2C%20Drelich%2C%20A.%2C%20Skinner%2C%20D.%2C%20Li%2C%20L.%20F.%2C%20Meek%2C%20T.%20D.%2C%20McKerrow%2C%20J.%20H.%2C%20Hook%2C%20V.%2C%20Tseng%2C%20C.%20T.%2C%20Larance%2C%20M.%2C%20Turville%2C%20S.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26%23x2026%3B%20Payne%2C%20R.%20J.%20%282022%29.%20Potent%20Anti-SARS-CoV-2%20Activity%20by%20the%20Natural%20Product%20Gallinamide%20A%20and%20Analogues%20via%20Inhibition%20of%20Cathepsin%20L.%20%3Ci%3EJournal%20of%20Medicinal%20Chemistry%3C%5C%2Fi%3E%2C%20%3Ci%3E65%3C%5C%2Fi%3E%284%29%2C%202956%26%23x2013%3B2970.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jmedchem.1c01494%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jmedchem.1c01494%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Potent%20Anti-SARS-CoV-2%20Activity%20by%20the%20Natural%20Product%20Gallinamide%20A%20and%20Analogues%20via%20Inhibition%20of%20Cathepsin%20L%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20S.%22%2C%22lastName%22%3A%22Ashhurst%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20H.%22%2C%22lastName%22%3A%22Tang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%22%2C%22lastName%22%3A%22Fajtova%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20C.%22%2C%22lastName%22%3A%22Yoon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Aggarwal%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20J.%22%2C%22lastName%22%3A%22Bedding%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Stoye%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Beretta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%22%2C%22lastName%22%3A%22Pwee%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Drelich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%22%2C%22lastName%22%3A%22Skinner%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%20F.%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%20D.%22%2C%22lastName%22%3A%22Meek%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20H.%22%2C%22lastName%22%3A%22McKerrow%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22V.%22%2C%22lastName%22%3A%22Hook%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20T.%22%2C%22lastName%22%3A%22Tseng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%22%2C%22lastName%22%3A%22Larance%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Turville%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22O%27Donoghue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%20J.%22%2C%22lastName%22%3A%22Payne%22%7D%5D%2C%22abstractNote%22%3A%22Cathepsin%20L%20is%20a%20key%20host%20cysteine%20protease%20utilized%20by%20coronaviruses%20for%20cell%20entry%20and%20is%20a%20promising%20drug%20target%20for%20novel%20antivirals%20against%20SARS-CoV-2.%20The%20marine%20natural%20product%20gallinamide%20A%20and%20several%20synthetic%20analogues%20were%20identified%20as%20potent%20inhibitors%20of%20cathepsin%20L%20with%20IC50%20values%20in%20the%20picomolar%20range.%20Lead%20molecules%20possessed%20selectivity%20over%20other%20cathepsins%20and%20alternative%20host%20proteases%20involved%20in%20viral%20entry.%20Gallinamide%20A%20directly%20interacted%20with%20cathepsin%20L%20in%20cells%20and%2C%20together%20with%20two%20lead%20analogues%2C%20potently%20inhibited%20SARS-CoV-2%20infection%20in%20vitro%2C%20with%20EC50%20values%20in%20the%20nanomolar%20range.%20Reduced%20antiviral%20activity%20was%20observed%20in%20cells%20overexpressing%20transmembrane%20protease%2C%20serine%202%20%28TMPRSS2%29%3B%20however%2C%20a%20synergistic%20improvement%20in%20antiviral%20activity%20was%20achieved%20when%20combined%20with%20a%20TMPRSS2%20inhibitor.%20These%20data%20highlight%20the%20potential%20of%20cathepsin%20L%20as%20a%20COVID-19%20drug%20target%20as%20well%20as%20the%20likely%20need%20to%20inhibit%20multiple%20routes%20of%20viral%20entry%20to%20achieve%20efficacy.%22%2C%22date%22%3A%222022%5C%2F02%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.jmedchem.1c01494%22%2C%22ISSN%22%3A%220022-2623%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A42Z%22%7D%7D%2C%7B%22key%22%3A%22KG3IE3AJ%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Yoon%20et%20al.%22%2C%22parsedDate%22%3A%222022-02%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EYoon%2C%20M.%20C.%2C%20Christy%2C%20M.%20P.%2C%20Phan%2C%20V.%20V.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20Hook%2C%20G.%2C%20O%26%23x2019%3BDonoghue%2C%20A.%20J.%2C%20%26amp%3B%20Hook%2C%20V.%20%282022%29.%20Molecular%20features%20of%20CA-074%20pH-dependent%20inhibition%20of%20Cathepsin%20B.%20%3Ci%3EBiochemistry%3C%5C%2Fi%3E%2C%20%3Ci%3E61%3C%5C%2Fi%3E%284%29%2C%20228%26%23x2013%3B238.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.biochem.1c00684%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.biochem.1c00684%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Molecular%20features%20of%20CA-074%20pH-dependent%20inhibition%20of%20Cathepsin%20B%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20C.%22%2C%22lastName%22%3A%22Yoon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20P.%22%2C%22lastName%22%3A%22Christy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22V.%20V.%22%2C%22lastName%22%3A%22Phan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%22%2C%22lastName%22%3A%22Hook%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22O%27Donoghue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22V.%22%2C%22lastName%22%3A%22Hook%22%7D%5D%2C%22abstractNote%22%3A%22CA-074%20is%20a%20selective%20inhibitor%20of%20cathepsin%20B%2C%20a%20lysosomal%20cysteine%20protease.%20CA-074%20has%20been%20utilized%20in%20numerous%20studies%20to%20demonstrate%20the%20role%20of%20this%20protease%20in%20cellular%20and%20physiological%20functions.%20Cathepsin%20B%20in%20numerous%20human%20disease%20mechanisms%20involves%20its%20translocation%20from%20acidic%20lysosomes%20of%20pH%204.6%20to%20neutral%20pH%207.2%20of%20cellular%20locations%2C%20including%20the%20cytosol%20and%20extracellular%20environment.%20To%20gain%20in-depth%20knowledge%20of%20CA-074%20inhibition%20under%20these%20different%20pH%20conditions%2C%20this%20study%20evaluated%20the%20molecular%20features%2C%20potency%2C%20and%20selectivity%20of%20CA-074%20for%20cathepsin%20B%20inhibition%20under%20acidic%20and%20neutral%20pH%20conditions.%20This%20study%20demonstrated%20that%20CA-074%20is%20most%20effective%20at%20inhibiting%20cathepsin%20B%20at%20an%20acidic%20pH%20of%204.6%20with%20nM%20potency%2C%20which%20was%20more%20than%20100-fold%20more%20potent%20than%20its%20inhibition%20at%20a%20neutral%20pH%20of%207.2.%20The%20pH-dependent%20inhibition%20of%20CA-074%20was%20abolished%20by%20methylation%20of%20its%20C-terminal%20proline%2C%20indicating%20the%20requirement%20for%20the%20free%20C-terminal%20carboxyl%20group%20for%20pH-dependent%20inhibition.%20Under%20these%20acidic%20and%20neutral%20pH%20conditions%2C%20CA-074%20maintained%20its%20specificity%20for%20cathepsin%20B%20over%20other%20cysteine%20cathepsins%2C%20displayed%20irreversible%20inhibition%2C%20and%20inhibited%20diverse%20cleavages%20of%20peptide%20substrates%20of%20cathepsin%20B%20assessed%20by%20profiling%20mass%20spectrometry.%20Molecular%20docking%20suggested%20that%20pH-dependent%20ionic%20interactions%20of%20the%20C-terminal%20carboxylate%20of%20CA%20-074%20occur%20with%20His110%20and%20His111%20residues%20in%20the%20S2%20%27%20subsite%20of%20the%20enzyme%20at%20pH%204.6%2C%20but%20these%20interactions%20differ%20at%20pH%207.2.%20While%20high%20levels%20of%20CA-074%20or%20CA-074Me%20%28converted%20by%20cellular%20esterases%20to%20CA-074%29%20are%20used%20in%20biological%20studies%20to%20inhibit%20cathepsin%20B%20at%20both%20acidic%20and%20neutral%20pH%20locations%2C%20it%20is%20possible%20that%20adjusted%20levels%20of%20CA-074%20or%20CA-074Me%20may%20be%20explored%20to%20differentially%20affect%20cathepsin%20B%20activity%20at%20these%20different%20pH%20values.%20Overall%2C%20the%20results%20of%20this%20study%20demonstrate%20the%20molecular%2C%20kinetic%2C%20and%20protease%20specificity%20features%20of%20CA-074%20pH-dependent%20inhibition%20of%20cathepsin%20B.%22%2C%22date%22%3A%222022%5C%2F02%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.biochem.1c00684%22%2C%22ISSN%22%3A%220006-2960%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A39Z%22%7D%7D%2C%7B%22key%22%3A%22Y6LYHYA9%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ottilie%20et%20al.%22%2C%22parsedDate%22%3A%222022-02%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EOttilie%2C%20S.%2C%20Luth%2C%20M.%20R.%2C%20Hellemann%2C%20E.%2C%20Goldgof%2C%20G.%20M.%2C%20Vigil%2C%20E.%2C%20Kumar%2C%20P.%2C%20Cheung%2C%20A.%20L.%2C%20Song%2C%20M.%2C%20Godinez-Macias%2C%20K.%20P.%2C%20Carolino%2C%20K.%2C%20Yang%2C%20J.%2C%20Lopez%2C%20G.%2C%20Abraham%2C%20M.%2C%20Tarsio%2C%20M.%2C%20LeBlanc%2C%20E.%2C%20Whitesell%2C%20L.%2C%20Schenken%2C%20J.%2C%20Gunawan%2C%20F.%2C%20Patel%2C%20R.%2C%20%26%23x2026%3B%20Winzeler%2C%20E.%20A.%20%282022%29.%20Adaptive%20laboratory%20evolution%20in%20S.%20cerevisiae%20highlights%20role%20of%20transcription%20factors%20in%20fungal%20xenobiotic%20resistance.%20%3Ci%3ECommunications%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E5%3C%5C%2Fi%3E%281%29%2C%2014.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs42003-022-03076-7%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs42003-022-03076-7%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Adaptive%20laboratory%20evolution%20in%20S.%20cerevisiae%20highlights%20role%20of%20transcription%20factors%20in%20fungal%20xenobiotic%20resistance%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Ottilie%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20R.%22%2C%22lastName%22%3A%22Luth%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Hellemann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%20M.%22%2C%22lastName%22%3A%22Goldgof%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Vigil%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%22%2C%22lastName%22%3A%22Kumar%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20L.%22%2C%22lastName%22%3A%22Cheung%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%22%2C%22lastName%22%3A%22Song%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%20P.%22%2C%22lastName%22%3A%22Godinez-Macias%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%22%2C%22lastName%22%3A%22Carolino%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%22%2C%22lastName%22%3A%22Lopez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%22%2C%22lastName%22%3A%22Abraham%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%22%2C%22lastName%22%3A%22Tarsio%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22LeBlanc%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Whitesell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Schenken%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22F.%22%2C%22lastName%22%3A%22Gunawan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Patel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Smith%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20S.%22%2C%22lastName%22%3A%22Love%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%20M.%22%2C%22lastName%22%3A%22Williams%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20W.%22%2C%22lastName%22%3A%22McNamara%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%22%2C%22lastName%22%3A%22Ideker%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Suzuki%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%20F.%22%2C%22lastName%22%3A%22Wirth%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20K.%22%2C%22lastName%22%3A%22Lukens%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%20M.%22%2C%22lastName%22%3A%22Kane%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%20E.%22%2C%22lastName%22%3A%22Cowen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20D.%22%2C%22lastName%22%3A%22Durrant%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%20A.%22%2C%22lastName%22%3A%22Winzeler%22%7D%5D%2C%22abstractNote%22%3A%22Ottilie%20et%20al.%20employ%20an%20experimental%20evolution%20approach%20to%20investigate%20the%20role%20of%20transcription%20factors%20in%20yeast%20chemical%20resistance.%20Most%20emergent%20mutations%20in%20resistant%20strains%20were%20enriched%20in%20transcription%20factor%20coding%20genes%2C%20highlighting%20their%20importance%20in%20drug%20resistance.%20In%20vitro%20evolution%20and%20whole%20genome%20analysis%20were%20used%20to%20comprehensively%20identify%20the%20genetic%20determinants%20of%20chemical%20resistance%20in%20Saccharomyces%20cerevisiae.%20Sequence%20analysis%20identified%20many%20genes%20contributing%20to%20the%20resistance%20phenotype%20as%20well%20as%20numerous%20amino%20acids%20in%20potential%20targets%20that%20may%20play%20a%20role%20in%20compound%20binding.%20Our%20work%20shows%20that%20compound-target%20pairs%20can%20be%20conserved%20across%20multiple%20species.%20The%20set%20of%2025%20most%20frequently%20mutated%20genes%20was%20enriched%20for%20transcription%20factors%2C%20and%20for%20almost%2025%20percent%20of%20the%20compounds%2C%20resistance%20was%20mediated%20by%20one%20of%20100%20independently%20derived%2C%20gain-of-function%20SNVs%20found%20in%20a%20170%20amino%20acid%20domain%20in%20the%20two%20Zn2C6%20transcription%20factors%20YRR1%20and%20YRM1%20%28p%20%3C%201%20x%2010%28-100%29%29.%20This%20remarkable%20enrichment%20for%20transcription%20factors%20as%20drug%20resistance%20genes%20highlights%20their%20important%20role%20in%20the%20evolution%20of%20antifungal%20xenobiotic%20resistance%20and%20underscores%20the%20challenge%20to%20develop%20antifungal%20treatments%20that%20maintain%20potency.%22%2C%22date%22%3A%222022%5C%2F02%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1038%5C%2Fs42003-022-03076-7%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A21Z%22%7D%7D%2C%7B%22key%22%3A%22K23CBFNL%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Kim%20et%20al.%22%2C%22parsedDate%22%3A%222022-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EKim%2C%20G.%20J.%2C%20Mascuch%2C%20S.%20J.%2C%20Mevers%2C%20E.%2C%20Boudreau%2C%20P.%20D.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Choi%2C%20H.%20%282022%29.%20Luquilloamides%2C%20cytotoxic%20lipopeptides%20from%20a%20puerto%20rican%20collection%20of%20the%20filamentous%20marine%20cyanobacterium%20Oscillatoria%20sp.%20%3Ci%3EJournal%20of%20Organic%20Chemistry%3C%5C%2Fi%3E%2C%2013.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.joc.1c02340%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.joc.1c02340%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Luquilloamides%2C%20cytotoxic%20lipopeptides%20from%20a%20puerto%20rican%20collection%20of%20the%20filamentous%20marine%20cyanobacterium%20Oscillatoria%20sp%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%20J.%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%20J.%22%2C%22lastName%22%3A%22Mascuch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Mevers%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%20D.%22%2C%22lastName%22%3A%22Boudreau%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%22%2C%22lastName%22%3A%22Choi%22%7D%5D%2C%22abstractNote%22%3A%22Luquilloamides%20A-G%20%281-7%29%20were%20isolated%20from%20a%20small%20environmental%20collection%20of%20a%20marine%20cyanobacterium%20found%20growing%20on%20eelgrass%20%28Zostera%20sp.%29%20near%20Luquillo%2C%20Puerto%20Rico.%20Structure%20elucidation%20of%20the%20luquilloamides%20was%20accomplished%20via%20detailed%20NMR%20and%20MS%20analyses%2C%20and%20absolute%20configurations%20were%20determined%20using%20a%20combination%20of%20advanced%20Mosher%27s%20method%2C%20J-based%20configuration%20analysis%2C%20semisynthetic%20fragment%20analysis%20derived%20from%20ozonolysis%2C%20methylation%2C%20Baeyer-Villiger%20oxidation%2C%20Mosher%27s%20esterification%2C%20specific%20rotations%2C%20and%20ECD%20data.%20Except%20for%202%2C%20the%20luquilloamides%20share%20a%20characteristic%20tert-butyl-containing%20polyketide%20fragment%2C%20beta-alanine%2C%20and%20a%20proposed%20highly%20modified%20polyketide%20extension.%20While%20compound%201%20is%20a%20linear%20lipopeptide%20with%20two%20amethyl%20branches%20and%20a%20vinyl%20chloride%20functionality%20in%20the%20polyketide%20portion%2C%20compounds%204%2C%206%2C%20and%207%20possess%20a%20cyclohexanone%20structure%20with%20methylation%20on%20the%20alpha-%20or%20beta-positions%20of%20the%20polyketide%20as%20well%20as%20an%20acetyl%20group.%20Interestingly%2C%20the%20absolute%20configuration%20at%20C-5%20and%20C-6%20on%20the%20cyclohexanone%20unit%20in%207%20is%20opposite%20to%20that%20of%204-6.%20Compound%203%20was%20revealed%20to%20have%20a%20tert-butyl-containing%20polyketide%2C%20beta-alanine%2C%20and%20a%20PKS%5C%2FNRPS-derived%20gamma-isopropyl%20pyrrolinone.%20Compound%202%20may%20be%20a%20hydrolysis%20product%20of%203.%20Of%20the%20seven%20new%20compounds%2C%201%20showed%20the%20most%20potent%20cytotoxicity%20to%20human%20H-460%20lung%20cancer%20cells.%22%2C%22date%22%3A%222022%5C%2F01%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.joc.1c02340%22%2C%22ISSN%22%3A%220022-3263%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A37Z%22%7D%7D%2C%7B%22key%22%3A%22HSCQAW8W%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Kim%20et%20al.%22%2C%22parsedDate%22%3A%222021-12%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EKim%2C%20H.%20W.%2C%20Zhang%2C%20C.%2C%20Cottrell%2C%20G.%20W.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282021%29.%20SMART-Miner%3A%20A%20convolutional%20neural%20network-based%20metabolite%20identification%20from%20H-1-C-13%20HSQC%20spectra.%20%3Ci%3EMagnetic%20Resonance%20in%20Chemistry%3C%5C%2Fi%3E%2C%206.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fmrc.5240%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fmrc.5240%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22SMART-Miner%3A%20A%20convolutional%20neural%20network-based%20metabolite%20identification%20from%20H-1-C-13%20HSQC%20spectra%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%20W.%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%20W.%22%2C%22lastName%22%3A%22Cottrell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22The%20identification%20of%20metabolites%20from%20complex%20biofluids%20and%20extracts%20of%20tissues%20is%20an%20essential%20process%20for%20understanding%20metabolic%20profiles.%20Nuclear%20magnetic%20resonance%20%28NMR%29%20spectroscopy%20is%20widely%20used%20in%20metabolomics%20studies%20for%20identification%20and%20quantification%20of%20metabolites.%20However%2C%20the%20accurate%20identification%20of%20individual%20metabolites%20is%20still%20a%20challenging%20process%20with%20higher%20peak%20intensity%20or%20similar%20chemical%20shifts%20from%20different%20metabolites.%20In%20this%20study%2C%20we%20applied%20a%20convolutional%20neural%20network%20%28CNN%29%20to%20H-1-C-13%20HSQC%20NMR%20spectra%20to%20achieve%20accurate%20peak%20identification%20in%20complex%20mixtures.%20The%20results%20reveal%20that%20the%20neural%20network%20was%20successfully%20trained%20on%20metabolite%20identification%20from%20these%202D%20NMR%20spectra%20and%20achieved%20very%20good%20performance%20compared%20with%20other%20NMR-based%20metabolomic%20tools.%22%2C%22date%22%3A%222021%5C%2F12%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1002%5C%2Fmrc.5240%22%2C%22ISSN%22%3A%220749-1581%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A44Z%22%7D%7D%2C%7B%22key%22%3A%22VSML7NJF%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Kim%20et%20al.%22%2C%22parsedDate%22%3A%222021-11%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EKim%2C%20H.%20W.%2C%20Wang%2C%20M.%20X.%2C%20Leber%2C%20C.%20A.%2C%20Nothias%2C%20L.%20F.%2C%20Reher%2C%20R.%2C%20Kang%2C%20K.%20B.%2C%20van%20der%20Hooft%2C%20J.%20J.%20J.%2C%20Dorrestein%2C%20P.%20C.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Cottrell%2C%20G.%20W.%20%282021%29.%20NPClassifier%3A%20A%20Deep%20Neural%20Network-Based%20Structural%20Classification%20Tool%20for%20Natural%20Products.%20%3Ci%3EJournal%20of%20Natural%20Products%3C%5C%2Fi%3E%2C%20%3Ci%3E84%3C%5C%2Fi%3E%2811%29%2C%202795%26%23x2013%3B2807.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.1c00399%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.1c00399%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22NPClassifier%3A%20A%20Deep%20Neural%20Network-Based%20Structural%20Classification%20Tool%20for%20Natural%20Products%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%20W.%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20X.%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20A.%22%2C%22lastName%22%3A%22Leber%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%20F.%22%2C%22lastName%22%3A%22Nothias%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Reher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%20B.%22%2C%22lastName%22%3A%22Kang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20J.%20J.%22%2C%22lastName%22%3A%22van%20der%20Hooft%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%20C.%22%2C%22lastName%22%3A%22Dorrestein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%20W.%22%2C%22lastName%22%3A%22Cottrell%22%7D%5D%2C%22abstractNote%22%3A%22Computational%20approaches%20such%20as%20genome%20and%20metabolome%20mining%20are%20becoming%20essential%20to%20natural%20products%20%28NPs%29%20research.%20Consequently%2C%20a%20need%20exists%20for%20an%20automated%20structure-type%20classification%20system%20to%20handle%20the%20massive%20amounts%20of%20data%20appearing%20for%20NP%20structures.%20An%20ideal%20semantic%20ontology%20for%20the%20classification%20of%20NPs%20should%20go%20beyond%20the%20simple%20presence%5C%2Fabsence%20of%20chemical%20substructures%2C%20but%20also%20include%20the%20taxonomy%20of%20the%20producing%20organism%2C%20the%20nature%20of%20the%20biosynthetic%20pathway%2C%20and%5C%2For%20their%20biological%20properties.%20Thus%2C%20a%20holistic%20and%20automatic%20NP%20classification%20framework%20could%20have%20considerable%20value%20to%20comprehensively%20navigate%20the%20relatedness%20of%20NPs%2C%20and%20especially%20so%20when%20analyzing%20large%20numbers%20of%20NPs.%20Here%2C%20we%20introduce%20NPClassifier%2C%20a%20deep-learning%20tool%20for%20the%20automated%20structural%20classification%20of%20NPs%20from%20their%20counted%20Morgan%20fingerprints.%20NPClassifier%20is%20expected%20to%20accelerate%20and%20enhance%20NP%20discovery%20by%20linking%20NP%20structures%20to%20their%20underlying%20properties.%22%2C%22date%22%3A%222021%5C%2F11%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.jnatprod.1c00399%22%2C%22ISSN%22%3A%220163-3864%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A40Z%22%7D%7D%2C%7B%22key%22%3A%22MIDPT7QU%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Almaliti%20et%20al.%22%2C%22parsedDate%22%3A%222021-11%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EAlmaliti%2C%20J.%2C%20Fajtova%2C%20P.%2C%20O%26%23x2019%3BDonoghue%2C%20A.%20J.%2C%20AlHindy%2C%20M.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282021%29.%20Improved%20scalable%20synthesis%20of%20clinical%20candidate%20KZR-616%2C%20a%20selective%20immunoproteasome%20inhibitor.%20%3Ci%3EChemistryselect%3C%5C%2Fi%3E%2C%20%3Ci%3E6%3C%5C%2Fi%3E%2844%29%2C%2012461%26%23x2013%3B12465.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fslct.202103455%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Fslct.202103455%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Improved%20scalable%20synthesis%20of%20clinical%20candidate%20KZR-616%2C%20a%20selective%20immunoproteasome%20inhibitor%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Almaliti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%22%2C%22lastName%22%3A%22Fajtova%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22O%27Donoghue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%22%2C%22lastName%22%3A%22AlHindy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22KZR-616%20is%20a%20selective%20immunoproteasome%20inhibitor%20that%20is%20under%20clinical%20evaluation%20for%20the%20treatment%20of%20Systemic%20Lupus%20Erythematosus%20%28SLE%29.%20KZR-616%20represents%20a%20first-in-class%20drug%20candidate%20for%20the%20treatment%20of%20autoimmune%20diseases%20targeting%20the%20immunoproteasome.%20Laboratory%20replication%20of%20the%20published%20synthetic%20route%20of%20KZR-616%20resulted%20in%20an%20inseparable%20mixture%20of%20enantiomers%20and%20diastereomers.%20Herein%2C%20we%20describe%20a%20stereoselective%20and%20scalable%20synthetic%20pathway%20for%20KZR-616%20that%20avoids%20laborious%20separation%20of%20enantiomeric%20mixtures%20of%20amino%20acids.%20Moreover%2C%20the%20new%20route%20provides%20KZR-616%20in%20higher%20overall%20yield%20%2842.8%20%25%29%2C%20did%20not%20require%20a%20chiral%20chromatographic%20purification%20step%2C%20and%20the%20final%20product%20was%20obtained%20in%20high%20purity.%20The%20synthesized%20compound%20was%20evaluated%20for%20inhibition%20of%20human%20immunoproteasome%20and%20constitutive%20proteasome%20and%20found%20to%20target%20the%20beta%201%20and%20beta%205%20subunits%20of%20the%20immunoproteasome%20with%20higher%20potency%20than%20the%20equivalent%20subunits%20of%20the%20constitutive%20proteasome.%20Therefore%2C%20we%20have%20confirmed%20that%20KZR-616%2C%20synthesized%20using%20this%20new%20method%2C%20is%20an%20immunoproteasome%20selective%20inhibitor.%22%2C%22date%22%3A%222021%5C%2F11%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1002%5C%2Fslct.202103455%22%2C%22ISSN%22%3A%222365-6549%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A34Z%22%7D%7D%2C%7B%22key%22%3A%22T89ZRRTG%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Yoon%20et%20al.%22%2C%22parsedDate%22%3A%222021-09%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EYoon%2C%20M.%20C.%2C%20Solania%2C%20A.%2C%20Jiang%2C%20Z.%20Z.%2C%20Christy%2C%20M.%20P.%2C%20Podvin%2C%20S.%2C%20Mosier%2C%20C.%2C%20Lietz%2C%20C.%20B.%2C%20Ito%2C%20G.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20Wolan%2C%20D.%20W.%2C%20Hook%2C%20G.%2C%20O%26%23x2019%3BDonoghue%2C%20A.%20J.%2C%20%26amp%3B%20Hook%2C%20V.%20%282021%29.%20Selective%20neutral%20pH%20Inhibitor%20of%20Cathepsin%20B%20designed%20based%20on%20cleavage%20preferences%20at%20cytosolic%20and%20lysosomal%20pH%20conditions.%20%3Ci%3EAcs%20Chemical%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E16%3C%5C%2Fi%3E%289%29%2C%201628%26%23x2013%3B1643.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facschembio.1c00138%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facschembio.1c00138%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Selective%20neutral%20pH%20Inhibitor%20of%20Cathepsin%20B%20designed%20based%20on%20cleavage%20preferences%20at%20cytosolic%20and%20lysosomal%20pH%20conditions%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20C.%22%2C%22lastName%22%3A%22Yoon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Solania%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Z.%20Z.%22%2C%22lastName%22%3A%22Jiang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20P.%22%2C%22lastName%22%3A%22Christy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Podvin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%22%2C%22lastName%22%3A%22Mosier%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20B.%22%2C%22lastName%22%3A%22Lietz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%22%2C%22lastName%22%3A%22Ito%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%20W.%22%2C%22lastName%22%3A%22Wolan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%22%2C%22lastName%22%3A%22Hook%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22O%27Donoghue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22V.%22%2C%22lastName%22%3A%22Hook%22%7D%5D%2C%22abstractNote%22%3A%22Cathepsin%20B%20is%20a%20cysteine%20protease%20that%20normally%20functions%20within%20acidic%20lysosomes%20for%20protein%20degradation%2C%20but%20in%20numerous%20human%20diseases%2C%20cathepsin%20B%20translocates%20to%20the%20cytosol%20having%20neutral%20pH%20where%20the%20enzyme%20activates%20inflammation%20and%20cell%20death.%20Cathepsin%20B%20is%20active%20at%20both%20the%20neutral%20pH%207.2%20of%20the%20cytosol%20and%20the%20acidic%20pH%204.6%20within%20lysosomes.%20We%20evaluated%20the%20hypothesis%20that%20cathepsin%20B%20may%20possess%20pH-dependent%20cleavage%20preferences%20that%20can%20be%20utilized%20for%20design%20of%20a%20selective%20neutral%20pH%20inhibitor%20by%20%281%29%20analysis%20of%20differential%20cathepsin%20B%20cleavage%20profiles%20at%20neutral%20pH%20compared%20to%20acidic%20pH%20using%20multiplex%20substrate%20profiling%20by%20mass%20spectrometry%20%28MSP-MS%29%2C%20%282%29%20design%20of%20pH-selective%20peptide-7-amino-4-methylcoumarin%20%28AMC%29%20substrates%2C%20and%20%283%29%20design%20and%20validation%20of%20Z-Arg-Lysacyloxymethyl%20ketone%20%28AOMK%29%20as%20a%20selective%20neutral%20pH%20inhibitor.%20Cathepsin%20B%20displayed%20preferences%20for%20cleaving%20peptides%20with%20Arg%20in%20the%20P2%20position%20at%20pH%207.2%20and%20Glu%20in%20the%20P2%20position%20at%20pH%204.6%2C%20represented%20by%20its%20primary%20dipeptidyl%20carboxypeptidase%20and%20modest%20endopeptidase%20activity.%20These%20properties%20led%20to%20design%20of%20the%20substrate%20Z-Arg-Lys-AMC%20having%20neutral%20pH%20selectivity%2C%20and%20its%20modification%20with%20the%20AOMK%20warhead%20to%20result%20in%20the%20inhibitor%20Z-Arg-Lys-AOMK.%20This%20irreversible%20inhibitor%20displays%20nanomolar%20potency%20with%20100-fold%20selectivity%20for%20inhibition%20of%20cathepsin%20B%20at%20pH%207.2%20compared%20to%20pH%204.6%2C%20shows%20specificity%20for%20cathepsin%20B%20over%20other%20cysteine%20cathepsins%2C%20and%20is%20cell%20permeable%20and%20inhibits%20intracellular%20cathepsin%20B.%20These%20findings%20demonstrate%20that%20cathepsin%20B%20possesses%20pH-dependent%20cleavage%20properties%20that%20can%20lead%20to%20development%20of%20a%20potent%2C%20neutral%20pH%20inhibitor%20of%20this%20enzyme.%22%2C%22date%22%3A%222021%5C%2F09%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1021%5C%2Facschembio.1c00138%22%2C%22ISSN%22%3A%221554-8929%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A44Z%22%7D%7D%2C%7B%22key%22%3A%223J4QS2GI%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Iwasaki%20et%20al.%22%2C%22parsedDate%22%3A%222021-09%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EIwasaki%2C%20A.%2C%20Teranuma%2C%20K.%2C%20Kurisawa%2C%20N.%2C%20Rahmawati%2C%20Y.%2C%20Jeelani%2C%20G.%2C%20Nozaki%2C%20T.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Suenaga%2C%20K.%20%282021%29.%20First%20total%20synthesis%20and%20structure-activity%20relationship%20of%20iheyamide%20A%2C%20an%20antitrypanosomal%20linear%20peptide%20isolated%20from%20a%20Dapis%20sp.%20Marine%20cyanobacterium.%20%3Ci%3EJournal%20of%20Natural%20Products%3C%5C%2Fi%3E%2C%20%3Ci%3E84%3C%5C%2Fi%3E%289%29%2C%202587%26%23x2013%3B2593.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.1c00792%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.1c00792%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22First%20total%20synthesis%20and%20structure-activity%20relationship%20of%20iheyamide%20A%2C%20an%20antitrypanosomal%20linear%20peptide%20isolated%20from%20a%20Dapis%20sp.%20Marine%20cyanobacterium%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Iwasaki%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%22%2C%22lastName%22%3A%22Teranuma%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22N.%22%2C%22lastName%22%3A%22Kurisawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Rahmawati%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%22%2C%22lastName%22%3A%22Jeelani%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%22%2C%22lastName%22%3A%22Nozaki%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%22%2C%22lastName%22%3A%22Suenaga%22%7D%5D%2C%22abstractNote%22%3A%22Iheyamide%20A%20%281%29%20is%20an%20antitrypanosomal%20linear%20peptide%20isolated%20from%20a%20Dapis%20sp.%20marine%20cyanobacterium%20by%20our%20group%20in%202020%2C%20and%20based%20on%20structure-activity%20relationships%20of%20its%20natural%20analogues%2C%20the%20C-terminal%20pyrrolinone%20moiety%20has%20been%20identified%20as%20the%20phamacophore%20for%20its%20antiparasitic%20activity.%20Further%2C%20we%20isolated%20this%20pyrrolinone%20moiety%20by%20itself%20as%20a%20new%20natural%20product%20from%20the%20marine%20cyanobacterium%20and%20named%20it%20iheyanone%20%282%29.%20As%20expected%2C%20iheyanone%20%282%29%20showed%20antitrypanosomal%20activity%2C%20but%20its%20potency%20was%20weaker%20than%20iheyamide%20A%20%281%29.%20To%20clarify%20more%20detailed%20structure-activity%20relationships%2C%20we%20completed%20a%20total%20synthesis%20of%20iheyamide%20A%20%281%29%20along%20with%20iheyanone%20%282%29%20and%20evaluated%20the%20antitrypanosomal%20activities%20of%20several%20synthetic%20intermediates.%20As%20a%20result%2C%20we%20found%20that%20the%20longer%20the%20peptide%20chain%2C%20the%20stronger%20the%20antitrypanosomal%20activity.%20As%20iheyamide%20A%20%281%29%20showed%20selective%20toxicity%20against%20Trypanosoma%20brucei%20rhodesiense%2C%20these%20findings%20can%20provide%20design%20guidelines%20for%20antitrypanosomal%20drugs.%22%2C%22date%22%3A%222021%5C%2F09%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.jnatprod.1c00792%22%2C%22ISSN%22%3A%220163-3864%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A32Z%22%7D%7D%2C%7B%22key%22%3A%22PSMX8CUT%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Demirkiran%20et%20al.%22%2C%22parsedDate%22%3A%222021-08%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EDemirkiran%2C%20O.%2C%20Almaliti%2C%20J.%2C%20Leao%2C%20T.%2C%20Navarro%2C%20G.%2C%20Byrum%2C%20T.%2C%20Valeriote%2C%20F.%20A.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20L.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282021%29.%20Portobelamides%20A%20and%20B%20and%20Caciqueamide%2C%20Cytotoxic%20Peptidic%20Natural%20Products%20from%20a%20Caldora%20sp.%20Marine%20Cyanobacterium.%20%3Ci%3EJournal%20of%20Natural%20Products%3C%5C%2Fi%3E%2C%20%3Ci%3E84%3C%5C%2Fi%3E%288%29%2C%202081%26%23x2013%3B2093.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.0c01383%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.0c01383%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Portobelamides%20A%20and%20B%20and%20Caciqueamide%2C%20Cytotoxic%20Peptidic%20Natural%20Products%20from%20a%20Caldora%20sp.%20Marine%20Cyanobacterium%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22O.%22%2C%22lastName%22%3A%22Demirkiran%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Almaliti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%22%2C%22lastName%22%3A%22Leao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%22%2C%22lastName%22%3A%22Navarro%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%22%2C%22lastName%22%3A%22Byrum%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22F.%20A.%22%2C%22lastName%22%3A%22Valeriote%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22Three%20new%20compounds%2C%20portobelamides%20A%20and%20B%20%281%20and%202%29%2C%203-amino-2-methyl-7-octynoic%20acid%20%28AMOYA%29%20and%20hydroxyisovaleric%20acid%20%28Hiva%29%20containing%20cyclic%20depsipeptides%2C%20and%20one%20long%20chain%20lipopeptide%20caciqueamide%20%283%29%2C%20were%20isolated%20from%20a%20field-collection%20of%20a%20Caldora%20sp.%20marine%20cyanobacterium%20obtained%20from%20Panama%20as%20part%20of%20the%20Panama%20International%20Cooperative%20Biodiversity%20Group%20Program.%20Their%20planar%20structures%20were%20elucidated%20through%20analysis%20of%202D%20NMR%20and%20MS%20data%2C%20especially%20high%20resolution%20%28HR%29%20MS2%5C%2FMS3%20fragmentation%20methods.%20The%20absolute%20configurations%20of%20compounds%201%20and%202%20were%20deduced%20by%20traditional%20hydrolysis%2C%20derivative%20formation%2C%20and%20chromatographic%20analyses%20compared%20with%20standards.%20Portobelamide%20A%20%281%29%20showed%20good%20cytotoxicity%20against%20H-460%20human%20lung%20cancer%20cells%20%2833%25%20survival%20at%200.9%20mu%20M%29.%22%2C%22date%22%3A%222021%5C%2F08%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.jnatprod.0c01383%22%2C%22ISSN%22%3A%220163-3864%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%2C%22X8P588WG%22%5D%2C%22dateModified%22%3A%222022-08-05T16%3A05%3A23Z%22%7D%7D%2C%7B%22key%22%3A%22A5FRG7L4%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Kim%20et%20al.%22%2C%22parsedDate%22%3A%222021-08%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EKim%2C%20H.%20W.%2C%20Jeon%2C%20J.%20B.%2C%20Zhang%2C%20M.%2C%20Cho%2C%20H.%20M.%2C%20Ryu%2C%20B.%2C%20Lee%2C%20B.%20W.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Oh%2C%20W.%20K.%20%282021%29.%20SIRT1%20Activation%20Enhancing%208%2C3%20%26%23x2019%3B-Neolignans%20from%20the%20Twigs%20of%20Corylopsis%20coreana%20Uyeki.%20%3Ci%3EPlants-Basel%3C%5C%2Fi%3E%2C%20%3Ci%3E10%3C%5C%2Fi%3E%288%29%2C%2012.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fplants10081684%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fplants10081684%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22SIRT1%20Activation%20Enhancing%208%2C3%20%27-Neolignans%20from%20the%20Twigs%20of%20Corylopsis%20coreana%20Uyeki%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%20W.%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20B.%22%2C%22lastName%22%3A%22Jeon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%20M.%22%2C%22lastName%22%3A%22Cho%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%22%2C%22lastName%22%3A%22Ryu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%20W.%22%2C%22lastName%22%3A%22Lee%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20K.%22%2C%22lastName%22%3A%22Oh%22%7D%5D%2C%22abstractNote%22%3A%22Three%20undescribed%208%2C3%20%27-neolignans%2C%20corynol%20%281%29%2C%203-methoxy-corynol%20%282%29%20and%203%20%27-deoxy-corynol%20%283%29%2C%20together%20with%20two%20bergenin%20derivatives%2C%20three%20flavonoids%2C%20two%20hydrolysable%20tannins%20and%20six%20simple%20phenolic%20compounds%2C%20were%20isolated%20from%20the%20twigs%20of%20Corylopsis%20coreana%20Uyeki.%20The%20structures%20of%20the%208%2C3%20%27-neolignans%20were%20elucidated%20by%20analyzing%20their%20NMR%2C%20HRESIMS%20and%20ECD%20spectra.%20All%20the%20isolated%20compounds%20were%20evaluated%20for%20their%20SIRT1%20stimulatory%20activity%2C%20and%203%20%27-deoxy-corynol%20%283%29%20showed%20SIRT1%20stimulation%20activity.%20Furthermore%2C%20a%20docking%20study%20of%203%20was%20performed%20with%20three%20representative%20binding%20pockets%20of%20SIRT1.%22%2C%22date%22%3A%222021%5C%2F08%22%2C%22language%22%3A%22English%22%2C%22DOI%22%3A%2210.3390%5C%2Fplants10081684%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A44Z%22%7D%7D%2C%7B%22key%22%3A%222SY44QT9%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Taylor%20et%20al.%22%2C%22parsedDate%22%3A%222021-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ETaylor%2C%20K.%20S.%2C%20Zhang%2C%20C.%2C%20Glukhov%2C%20E.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Suyama%2C%20T.%20L.%20%282021%29.%20Total%20synthesis%20of%20laucysteinamide%20A%2C%20a%20monomeric%20congener%20of%20somocystinamide%20A.%20%3Ci%3EJournal%20of%20Natural%20Products%3C%5C%2Fi%3E%2C%20%3Ci%3E84%3C%5C%2Fi%3E%283%29%2C%20865%26%23x2013%3B870.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.0c01317%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.0c01317%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Total%20synthesis%20of%20laucysteinamide%20A%2C%20a%20monomeric%20congener%20of%20somocystinamide%20A%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%20S.%22%2C%22lastName%22%3A%22Taylor%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%20L.%22%2C%22lastName%22%3A%22Suyama%22%7D%5D%2C%22abstractNote%22%3A%22Laucysteinamide%20A%20%284%29%20is%20a%20marine%20natural%20product%20isolated%20from%20the%20cyanobacterium%20Caldora%20penicillata%20and%20contains%20structural%20motifs%20found%20in%20promising%20cancer%20drug%20leads.%20The%20first%20total%20synthesis%20of%204%20and%20its%20analogues%20was%20achieved%2C%20which%20also%20enabled%20a%20concise%20formal%20synthesis%20of%20somocystinamide%20A%20%283%29%2C%20a%20dimeric%20congener%20of%204%20that%20previously%20showed%20extremely%20potent%20antiproliferative%20activities.%20This%20work%20provides%20further%20insights%20on%20structure-activity%20relationships%20in%20this%20class%20of%20natural%20products.%22%2C%22date%22%3A%222021%5C%2F03%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.jnatprod.0c01317%22%2C%22ISSN%22%3A%220163-3864%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A48Z%22%7D%7D%2C%7B%22key%22%3A%22L47BI9RK%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Li%20et%20al.%22%2C%22parsedDate%22%3A%222021-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELi%2C%20L.%2C%20Yang%2C%20M.%2C%20Shrestha%2C%20S.%20K.%2C%20Kim%2C%20H.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Soh%2C%20Y.%20%282021%29.%20Kalkitoxin%20reduces%20osteoclast%20formation%20and%20resorption%20and%20protects%20against%20inflammatory%20bone%20loss.%20%3Ci%3EInternational%20Journal%20of%20Molecular%20Sciences%3C%5C%2Fi%3E%2C%20%3Ci%3E22%3C%5C%2Fi%3E%285%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fijms22052303%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fijms22052303%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Kalkitoxin%20reduces%20osteoclast%20formation%20and%20resorption%20and%20protects%20against%20inflammatory%20bone%20loss%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%20K.%22%2C%22lastName%22%3A%22Shrestha%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Soh%22%7D%5D%2C%22abstractNote%22%3A%22Osteoclasts%2C%20bone-specified%20multinucleated%20cells%20produced%20by%20monocyte%5C%2Fmacrophage%2C%20are%20involved%20in%20numerous%20bone%20destructive%20diseases%20such%20as%20arthritis%2C%20osteoporosis%2C%20and%20inflammation-induced%20bone%20loss.%20The%20osteoclast%20differentiation%20mechanism%20suggests%20a%20possible%20strategy%20to%20treat%20bone%20diseases.%20In%20this%20regard%2C%20we%20recently%20examined%20the%20in%20vivo%20impact%20of%20kalkitoxin%20%28KT%29%2C%20a%20marine%20product%20obtained%20from%20the%20marine%20cyanobacterium%20Moorena%20producens%20%28previously%20Lyngbya%20majuscula%29%2C%20on%20the%20macrophage%20colony-stimulating%20factor%20%28M-CSF%29%20and%20on%20the%20receptor%20activator%20of%20nuclear%20factor%20kappa%20B%20ligand%20%28RANKL%29-stimulated%20in%20vitro%20osteoclastogenesis%20and%20inflammation-mediated%20bone%20loss.%20We%20have%20now%20examined%20the%20molecular%20mechanism%20of%20KT%20in%20greater%20detail.%20KT%20decreased%20RANKL-induced%20bone%20marrow-derived%20macrophages%20%28BMMs%29%20tartrate-resistant%20acid%20phosphatase%20%28TRAP%29-multinucleated%20cells%20at%20a%20late%20stage.%20Likewise%2C%20KT%20suppressed%20RANKL-induced%20pit%20area%20and%20actin%20ring%20formation%20in%20BMM%20cells.%20Additionally%2C%20KT%20inhibited%20several%20RANKL-induced%20genes%20such%20as%20cathepsin%20K%2C%20matrix%20metalloproteinase%20%28MMP-9%29%2C%20TRAP%2C%20and%20dendritic%20cell-specific%20transmembrane%20protein%20%28DC-STAMP%29.%20In%20line%20with%20these%20results%2C%20RANKL%20stimulated%20both%20genes%20and%20protein%20expression%20of%20c-Fos%20and%20nuclear%20factor%20of%20activated%20T%20cells%20%28NFATc1%29%2C%20and%20this%20was%20also%20suppressed%20by%20KT.%20Moreover%2C%20KT%20markedly%20decreased%20RANKL-induced%20p-ERK1%5C%2F2%20and%20p-JNK%20pathways%20at%20different%20time%20points.%20As%20a%20result%2C%20KT%20prevented%20inflammatory%20bone%20loss%20in%20mice%2C%20such%20as%20bone%20mineral%20density%20%28BMD%29%20and%20osteoclast%20differentiation%20markers.%20These%20experiments%20demonstrated%20that%20KT%20markedly%20inhibited%20osteoclast%20formation%20and%20inflammatory%20bone%20loss%20through%20NFATc1%20and%20mitogen-activated%20protein%20kinase%20%28MAPK%29%20signaling%20pathways.%20Therefore%2C%20KT%20may%20have%20potential%20as%20a%20treatment%20for%20destructive%20bone%20diseases.%22%2C%22date%22%3A%222021%5C%2F03%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3390%5C%2Fijms22052303%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A36Z%22%7D%7D%2C%7B%22key%22%3A%22UNEIQ7TK%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Leber%20et%20al.%22%2C%22parsedDate%22%3A%222021-02%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELeber%2C%20C.%20A.%2C%20Reyes%2C%20A.%20J.%2C%20Biggs%2C%20J.%20S.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282021%29.%20Cyanobacteria-shrimp%20colonies%20in%20the%20Mariana%20Islands.%20%3Ci%3EAquatic%20Ecology%3C%5C%2Fi%3E.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1007%5C%2Fs10452-021-09837-6%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1007%5C%2Fs10452-021-09837-6%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Cyanobacteria-shrimp%20colonies%20in%20the%20Mariana%20Islands%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20A.%22%2C%22lastName%22%3A%22Leber%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22Reyes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20S.%22%2C%22lastName%22%3A%22Biggs%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22Cyanobacteria%20have%20multifaceted%20ecological%20roles%20on%20coral%20reefs.%20Moorena%20bouillonii%2C%20a%20chemically%20rich%20filamentous%20cyanobacterium%2C%20has%20been%20characterized%20as%20a%20pathogenic%20organism%20with%20an%20unusual%20ability%20to%20overgrow%20gorgonian%20corals%2C%20but%20little%20has%20been%20done%20to%20study%20its%20general%20growth%20habits%20or%20its%20unique%20association%20with%20the%20snapping%20shrimp%20Alpheus%20frontalis.%20Quantitative%20benthic%20surveys%2C%20and%20field%20and%20photographic%20observations%20were%20utilized%20to%20develop%20a%20better%20understanding%20of%20the%20ecology%20of%20these%20species%2C%20while%20growth%20experiments%20and%20nutrient%20analysis%20were%20performed%20to%20examine%20how%20this%20cyanobacterium%20may%20be%20benefiting%20from%20its%20shrimp%20symbiont.%20Colonies%20of%20M.%20bouillonii%20and%20A.%20frontalis%20displayed%20considerable%20habitat%20specificity%20in%20terms%20of%20occupied%20substrate.%20Although%20found%20to%20vary%20in%20abundance%20and%20density%20across%20survey%20sites%20and%20transects%2C%20M.%20bouillonii%20was%20consistently%20found%20to%20be%20thriving%20with%20A.%20frontalis%20within%20interstitial%20spaces%20on%20the%20reef.%20Removal%20of%20A.%20frontalis%20from%20cyanobacterial%20colonies%20in%20a%20laboratory%20experiment%20altered%20M.%20bouillonii%20pigmentation%2C%20whereas%20cyanobacteria-shrimp%20colonies%20in%20the%20field%20exhibited%20elevated%20nutrient%20levels%20compared%20to%20the%20surrounding%20seawater.%22%2C%22date%22%3A%222021%5C%2F02%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1007%5C%2Fs10452-021-09837-6%22%2C%22ISSN%22%3A%221386-2588%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A28Z%22%7D%7D%2C%7B%22key%22%3A%22RZBXJ2CY%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Christy%20et%20al.%22%2C%22parsedDate%22%3A%222021-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EChristy%2C%20M.%20P.%2C%20Uekusa%2C%20Y.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20L.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282021%29.%20Natural%20products%20with%20potential%20to%20treat%20RNA%20virus%20pathogens%20including%20SARS-CoV-2.%20%3Ci%3EJournal%20of%20Natural%20Products%3C%5C%2Fi%3E%2C%20%3Ci%3E84%3C%5C%2Fi%3E%281%29%2C%20161%26%23x2013%3B182.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.0c00968%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.0c00968%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Natural%20products%20with%20potential%20to%20treat%20RNA%20virus%20pathogens%20including%20SARS-CoV-2%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20P.%22%2C%22lastName%22%3A%22Christy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Uekusa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22Three%20families%20of%20RNA%20viruses%2C%20the%20Coronaviridae%2C%20Flaviviridae%2C%20and%20Filoviridae%2C%20collectively%20have%20great%20potential%20to%20cause%20epidemic%20disease%20in%20human%20populations.%20The%20current%20SARS-CoV-2%20%28Coronaviridae%29%20responsible%20for%20the%20COVID-19%20pandemic%20underscores%20the%20lack%20of%20effective%20medications%20currently%20available%20to%20treat%20these%20classes%20of%20viral%20pathogens.%20Similarly%2C%20the%20Flaviviridae%2C%20which%20includes%20such%20viruses%20as%20Dengue%2C%20West%20Nile%2C%20and%20Zika%2C%20and%20the%20Filoviridae%2C%20with%20the%20Ebola-type%20viruses%2C%20as%20examples%2C%20all%20lack%20effective%20therapeutics.%20In%20this%20review%2C%20we%20present%20fundamental%20information%20concerning%20the%20biology%20of%20these%20three%20virus%20families%2C%20including%20their%20genomic%20makeup%2C%20mode%20of%20infection%20of%20human%20cells%2C%20and%20key%20proteins%20that%20may%20offer%20targeted%20therapies.%20Further%2C%20we%20present%20the%20natural%20products%20and%20their%20derivatives%20that%20have%20documented%20activities%20to%20these%20viral%20and%20host%20proteins%2C%20offering%20hope%20for%20future%20mechanism-based%20antiviral%20therapeutics.%20By%20arranging%20these%20potential%20protein%20targets%20and%20their%20natural%20product%20inhibitors%20by%20target%20type%20across%20these%20three%20families%20of%20virus%2C%20new%20insights%20are%20developed%2C%20and%20crossover%20treatment%20strategies%20are%20suggested.%20Hence%2C%20natural%20products%2C%20as%20is%20the%20case%20for%20other%20therapeutic%20areas%2C%20continue%20to%20be%20a%20promising%20source%20of%20structurally%20diverse%20new%20anti-RNA%20virus%20therapeutics.%22%2C%22date%22%3A%222021%5C%2F01%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.jnatprod.0c00968%22%2C%22ISSN%22%3A%220163-3864%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%2C%22X8P588WG%22%5D%2C%22dateModified%22%3A%222022-08-05T16%3A11%3A11Z%22%7D%7D%2C%7B%22key%22%3A%22LIJGHBZ5%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Leao%20et%20al.%22%2C%22parsedDate%22%3A%222021-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELeao%2C%20T.%2C%20Wang%2C%20M.%20X.%2C%20Moss%2C%20N.%2C%20da%20Silva%2C%20R.%2C%20Sanders%2C%20J.%2C%20Nurk%2C%20S.%2C%20Gurevich%2C%20A.%2C%20Humphrey%2C%20G.%2C%20Reher%2C%20R.%2C%20Zhu%2C%20Q.%20Y.%2C%20Belda-Ferre%2C%20P.%2C%20Glukhov%2C%20E.%2C%20Whitner%2C%20S.%2C%20Alexander%2C%20K.%20L.%2C%20Rex%2C%20R.%2C%20Pevzner%2C%20P.%2C%20Dorrestein%2C%20P.%20C.%2C%20Knight%2C%20R.%2C%20Bandeira%2C%20N.%2C%20%26%23x2026%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20L.%20%282021%29.%20A%20multi-omics%20characterization%20of%20the%20natural%20product%20potential%20of%20tropical%20filamentous%20marine%20cyanobacteria.%20%3Ci%3EMarine%20Drugs%3C%5C%2Fi%3E%2C%20%3Ci%3E19%3C%5C%2Fi%3E%281%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmd19010020%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmd19010020%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22A%20multi-omics%20characterization%20of%20the%20natural%20product%20potential%20of%20tropical%20filamentous%20marine%20cyanobacteria%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%22%2C%22lastName%22%3A%22Leao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20X.%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22N.%22%2C%22lastName%22%3A%22Moss%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22da%20Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Sanders%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Nurk%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Gurevich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%22%2C%22lastName%22%3A%22Humphrey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Reher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Q.%20Y.%22%2C%22lastName%22%3A%22Zhu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%22%2C%22lastName%22%3A%22Belda-Ferre%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Whitner%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%20L.%22%2C%22lastName%22%3A%22Alexander%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Rex%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%22%2C%22lastName%22%3A%22Pevzner%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%20C.%22%2C%22lastName%22%3A%22Dorrestein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Knight%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22N.%22%2C%22lastName%22%3A%22Bandeira%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22Microbial%20natural%20products%20are%20important%20for%20the%20understanding%20of%20microbial%20interactions%2C%20chemical%20defense%20and%20communication%2C%20and%20have%20also%20served%20as%20an%20inspirational%20source%20for%20numerous%20pharmaceutical%20drugs.%20Tropical%20marine%20cyanobacteria%20have%20been%20highlighted%20as%20a%20great%20source%20of%20new%20natural%20products%2C%20however%2C%20few%20reports%20have%20appeared%20wherein%20a%20multi-omics%20approach%20has%20been%20used%20to%20study%20their%20natural%20products%20potential%20%28i.e.%2C%20reports%20are%20often%20focused%20on%20an%20individual%20natural%20product%20and%20its%20biosynthesis%29.%20This%20study%20focuses%20on%20describing%20the%20natural%20product%20genetic%20potential%20as%20well%20as%20the%20expressed%20natural%20product%20molecules%20in%20benthic%20tropical%20cyanobacteria.%20We%20collected%20from%20several%20sites%20around%20the%20world%20and%20sequenced%20the%20genomes%20of%2024%20tropical%20filamentous%20marine%20cyanobacteria.%20The%20informatics%20program%20antiSMASH%20was%20used%20to%20annotate%20the%20major%20classes%20of%20gene%20clusters.%20BiG-SCAPE%20phylum-wide%20analysis%20revealed%20the%20most%20promising%20strains%20for%20natural%20product%20discovery%20among%20these%20cyanobacteria.%20LCMS%5C%2FMS-based%20metabolomics%20highlighted%20the%20most%20abundant%20molecules%20and%20molecular%20classes%20among%2010%20of%20these%20marine%20cyanobacterial%20samples.%20We%20observed%20that%20despite%20many%20genes%20encoding%20for%20peptidic%20natural%20products%2C%20peptides%20were%20not%20as%20abundant%20as%20lipids%20and%20lipopeptides%20in%20the%20chemical%20extracts.%20Our%20results%20highlight%20a%20number%20of%20highly%20interesting%20biosynthetic%20gene%20clusters%20for%20genome%20mining%20among%20these%20cyanobacterial%20samples.%22%2C%22date%22%3A%222021%5C%2F01%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3390%5C%2Fmd19010020%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%2C%22X8P588WG%22%5D%2C%22dateModified%22%3A%222022-07-27T16%3A54%3A11Z%22%7D%7D%2C%7B%22key%22%3A%226ZBLPD6G%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Taton%20et%20al.%22%2C%22parsedDate%22%3A%222020-12%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ETaton%2C%20A.%2C%20Ecker%2C%20A.%2C%20Diaz%2C%20B.%2C%20Moss%2C%20N.%20A.%2C%20Anderson%2C%20B.%2C%20Reher%2C%20R.%2C%20Leao%2C%20T.%20F.%2C%20Simkovsky%2C%20R.%2C%20Dorrestein%2C%20P.%20C.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20L.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Golden%2C%20J.%20W.%20%282020%29.%20Heterologous%20expression%20of%20cryptomaldamide%20in%20a%20cyanobacterial%20host.%20%3Ci%3EAcs%20Synthetic%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E9%3C%5C%2Fi%3E%2812%29%2C%203364%26%23x2013%3B3376.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facssynbio.0c00431%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facssynbio.0c00431%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Heterologous%20expression%20of%20cryptomaldamide%20in%20a%20cyanobacterial%20host%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Taton%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Ecker%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%22%2C%22lastName%22%3A%22Diaz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22N.%20A.%22%2C%22lastName%22%3A%22Moss%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%22%2C%22lastName%22%3A%22Anderson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Reher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%20F.%22%2C%22lastName%22%3A%22Leao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Simkovsky%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%20C.%22%2C%22lastName%22%3A%22Dorrestein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20W.%22%2C%22lastName%22%3A%22Golden%22%7D%5D%2C%22abstractNote%22%3A%22Filamentous%20marine%20cyanobacteria%20make%20a%20variety%20of%20bioactive%20molecules%20that%20are%20produced%20by%20polyketide%20synthases%2C%20nonribosomal%20peptide%20synthetases%2C%20and%20hybrid%20pathways%20that%20are%20encoded%20by%20large%20biosynthetic%20gene%20clusters.%20These%20cyanobacterial%20natural%20products%20represent%20potential%20drug%20leads%3B%20however%2C%20thorough%20pharmacological%20investigations%20have%20been%20impeded%20by%20the%20limited%20quantity%20of%20compound%20that%20is%20typically%20available%20from%20the%20native%20organisms.%20Additionally%2C%20investigations%20of%20the%20biosynthetic%20gene%20clusters%20and%20enzymatic%20pathways%20have%20been%20difficult%20due%20to%20the%20inability%20to%20conduct%20genetic%20manipulations%20in%20the%20native%20producers.%20Here%20we%20report%20a%20set%20of%20genetic%20tools%20for%20the%20heterologous%20expression%20of%20biosynthetic%20gene%20clusters%20in%20the%20cyanobacteria%20Synechococcus%20elongatus%20PCC%207942%20and%20Anabaena%20%28Nostoc%29%20PCC%207120.%20To%20facilitate%20the%20transfer%20of%20gene%20clusters%20in%20both%20strains%2C%20we%20engineered%20a%20strain%20of%20Anabaena%20that%20contains%20S.%20elongatus%20homologous%20sequences%20for%20chromosomal%20recombination%20at%20a%20neutral%20site%20and%20devised%20a%20CRISPR-based%20strategy%20to%20efficiently%20obtain%20segregated%20double%20recombinant%20clones%20of%20Anabaena.%20These%20genetic%20tools%20were%20used%20to%20express%20the%20large%2028.7%20kb%20cryptomaldamide%20biosynthetic%20gene%20cluster%20from%20the%20marine%20cyanobacterium%20Moorena%20%28Moorea%29%20producens%20JHB%20in%20both%20model%20strains.%20S.%20elongatus%20did%20not%20produce%20cryptomaldamide%3B%20however%2C%20high-titer%20production%20of%20cryptomaldamide%20was%20obtained%20in%20Anabaena.%20The%20methods%20developed%20in%20this%20study%20will%20facilitate%20the%20heterologous%20expression%20of%20biosynthetic%20gene%20clusters%20isolated%20from%20marine%20cyanobacteria%20and%20complex%20metagenomic%20samples.%22%2C%22date%22%3A%222020%5C%2F12%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1021%5C%2Facssynbio.0c00431%22%2C%22ISSN%22%3A%222161-5063%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%2C%22X8P588WG%22%5D%2C%22dateModified%22%3A%222022-08-15T17%3A42%3A22Z%22%7D%7D%2C%7B%22key%22%3A%224MG77L2X%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Li%20et%20al.%22%2C%22parsedDate%22%3A%222020-10%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELi%2C%20Y.%20Y.%2C%20Naman%2C%20C.%20B.%2C%20Alexander%2C%20K.%20L.%2C%20Guan%2C%20H.%20S.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282020%29.%20The%20chemistry%2C%20biochemistry%20and%20pharmacology%20of%20marine%20natural%20products%20from%20Leptolyngbya%2C%20a%20chemically%20endowed%20genus%20of%20cyanobacteria.%20%3Ci%3EMarine%20Drugs%3C%5C%2Fi%3E%2C%20%3Ci%3E18%3C%5C%2Fi%3E%2810%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmd18100508%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmd18100508%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22The%20chemistry%2C%20biochemistry%20and%20pharmacology%20of%20marine%20natural%20products%20from%20Leptolyngbya%2C%20a%20chemically%20endowed%20genus%20of%20cyanobacteria%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%20Y.%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20B.%22%2C%22lastName%22%3A%22Naman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%20L.%22%2C%22lastName%22%3A%22Alexander%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%20S.%22%2C%22lastName%22%3A%22Guan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22Leptolyngbya%2C%20a%20well-known%20genus%20of%20cyanobacteria%2C%20is%20found%20in%20various%20ecological%20habitats%20including%20marine%2C%20fresh%20water%2C%20swamps%2C%20and%20rice%20fields.%20Species%20of%20this%20genus%20are%20associated%20with%20many%20ecological%20phenomena%20such%20as%20nitrogen%20fixation%2C%20primary%20productivity%20through%20photosynthesis%20and%20algal%20blooms.%20As%20a%20result%2C%20there%20have%20been%20a%20number%20of%20investigations%20of%20the%20ecology%2C%20natural%20product%20chemistry%2C%20and%20biological%20characteristics%20of%20members%20of%20this%20genus.%20In%20general%2C%20the%20secondary%20metabolites%20of%20cyanobacteria%20are%20considered%20to%20be%20rich%20sources%20for%20drug%20discovery%20and%20development.%20In%20this%20review%2C%20the%20secondary%20metabolites%20reported%20in%20marine%20Leptolyngbya%20with%20their%20associated%20biological%20activities%20or%20interesting%20biosynthetic%20pathways%20are%20reviewed%2C%20and%20new%20insights%20and%20perspectives%20on%20their%20metabolic%20capacities%20are%20gained.%22%2C%22date%22%3A%222020%5C%2F10%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3390%5C%2Fmd18100508%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A27Z%22%7D%7D%2C%7B%22key%22%3A%22TKPKQZBM%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Leber%20et%20al.%22%2C%22parsedDate%22%3A%222020-10%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELeber%2C%20C.%20A.%2C%20Naman%2C%20C.%20B.%2C%20Keller%2C%20L.%2C%20Almaliti%2C%20J.%2C%20Caro-Diaz%2C%20E.%20J.%20E.%2C%20Glukhov%2C%20E.%2C%20Joseph%2C%20V.%2C%20Sajeevan%2C%20T.%20P.%2C%20Reyes%2C%20A.%20J.%2C%20Biggs%2C%20J.%20S.%2C%20Li%2C%20T.%2C%20Yuan%2C%20Y.%2C%20He%2C%20S.%2C%20Yan%2C%20X.%20J.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282020%29.%20Applying%20a%20chemogeographic%20strategy%20for%20natural%20product%20discovery%20from%20the%20marine%20cyanobacterium%20Moorena%20bouillonii.%20%3Ci%3EMarine%20Drugs%3C%5C%2Fi%3E%2C%20%3Ci%3E18%3C%5C%2Fi%3E%2810%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmd18100515%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmd18100515%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Applying%20a%20chemogeographic%20strategy%20for%20natural%20product%20discovery%20from%20the%20marine%20cyanobacterium%20Moorena%20bouillonii%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20A.%22%2C%22lastName%22%3A%22Leber%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20B.%22%2C%22lastName%22%3A%22Naman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Keller%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Almaliti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%20J.%20E.%22%2C%22lastName%22%3A%22Caro-Diaz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22V.%22%2C%22lastName%22%3A%22Joseph%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%20P.%22%2C%22lastName%22%3A%22Sajeevan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22Reyes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20S.%22%2C%22lastName%22%3A%22Biggs%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Yuan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22He%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22X.%20J.%22%2C%22lastName%22%3A%22Yan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22The%20tropical%20marine%20cyanobacterium%20Moorena%20bouillonii%20occupies%20a%20large%20geographic%20range%20across%20the%20Indian%20and%20Western%20Tropical%20Pacific%20Oceans%20and%20is%20a%20prolific%20producer%20of%20structurally%20unique%20and%20biologically%20active%20natural%20products.%20An%20ensemble%20of%20computational%20approaches%2C%20including%20the%20creation%20of%20the%20ORCA%20%28Objective%20Relational%20Comparative%20Analysis%29%20pipeline%20for%20flexible%20MS1%20feature%20detection%20and%20multivariate%20analyses%2C%20were%20used%20to%20analyze%20various%20M.%20bouillonii%20samples.%20The%20observed%20chemogeographic%20patterns%20suggested%20the%20production%20of%20regionally%20specific%20natural%20products%20by%20M.%20bouillonii.%20Analyzing%20the%20drivers%20of%20these%20chemogeographic%20patterns%20allowed%20for%20the%20identification%2C%20targeted%20isolation%2C%20and%20structure%20elucidation%20of%20a%20regionally%20specific%20natural%20product%2C%20doscadenamide%20A%20%281%29.%20Analyses%20of%20MS2%20fragmentation%20patterns%20further%20revealed%20this%20natural%20product%20to%20be%20part%20of%20an%20extensive%20family%20of%20herein%20annotated%2C%20proposed%20natural%20structural%20analogs%20%28doscadenamides%20B-J%2C%202-10%29%3B%20the%20ensemble%20of%20structures%20reflect%20a%20combinatorial%20biosynthesis%20using%20nonribosomal%20peptide%20synthetase%20%28NRPS%29%20and%20polyketide%20synthase%20%28PKS%29%20components.%20Compound%201%20displayed%20synergistic%20in%20vitro%20cancer%20cell%20cytotoxicity%20when%20administered%20with%20lipopolysaccharide%20%28LPS%29.%20These%20discoveries%20illustrate%20the%20utility%20in%20leveraging%20chemogeographic%20patterns%20for%20prioritizing%20natural%20product%20discovery%20efforts.%22%2C%22date%22%3A%222020%5C%2F10%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3390%5C%2Fmd18100515%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A23Z%22%7D%7D%2C%7B%22key%22%3A%22JRYXKVZ8%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Yang%20et%20al.%22%2C%22parsedDate%22%3A%222020-08%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EYang%2C%20J.%20M.%2C%20Liu%2C%20Y.%20Y.%2C%20Yang%2C%20W.%20C.%2C%20Ma%2C%20X.%20X.%2C%20Nie%2C%20Y.%20Y.%2C%20Glukhov%2C%20E.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20L.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20Lei%2C%20X.%20L.%2C%20%26amp%3B%20Zhang%2C%20Y.%20%282020%29.%20An%20anti-inflammatory%20isoflavone%20from%20soybean%20inoculated%20with%20a%20marine%20fungusAspergillus%20terreusC23-3.%20%3Ci%3EBioscience%20Biotechnology%20and%20Biochemistry%3C%5C%2Fi%3E%2C%20%3Ci%3E84%3C%5C%2Fi%3E%288%29%2C%201546%26%23x2013%3B1553.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1080%5C%2F09168451.2020.1764838%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1080%5C%2F09168451.2020.1764838%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22An%20anti-inflammatory%20isoflavone%20from%20soybean%20inoculated%20with%20a%20marine%20fungusAspergillus%20terreusC23-3%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20M.%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%20Y.%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20C.%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22X.%20X.%22%2C%22lastName%22%3A%22Ma%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%20Y.%22%2C%22lastName%22%3A%22Nie%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22X.%20L.%22%2C%22lastName%22%3A%22Lei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Zhang%22%7D%5D%2C%22abstractNote%22%3A%22A%20new%20isoflavone%20derivative%20compound1%28psoralenone%29%20was%20isolated%20from%20soybean%20inoculated%20with%20a%20marine%20fungusAspergillus%20terreusC23-3%2C%20together%20with%20seven%20known%20compounds%20including%20isoflavones2-6%2C%20butyrolactone%20I%20%287%29%20and%20blumenol%20A%20%288%29.%20Their%20structures%20were%20elucidated%20by%20MS%2C%20NMR%2C%20and%20ECD.%20Psoralenone%20displayed%20moderatein%20vitroanti-inflammatory%20activity%20in%20the%20LPS-induced%20RAW264.7%20cell%20model.%20Compound2%28genistein%29%20showed%20moderate%20acetylcholinesterase%20%28AChE%29%20inhibitory%20activity%20whereas%20compounds2%2C%205%28biochanin%20A%29%2C6%28psoralenol%29%2C%20and7exhibited%20potent%20larvicidal%20activity%20against%20brine%20shrimp.%20Compounds3%28daidzein%29%2C4%284MODIFIER%20LETTER%20PRIME-hydroxy-6%2C7-dimethoxyisoflavone%29%2C%20and5-7showed%20broad-spectrum%20anti-microbial%20activity%2C%20and%20compound7also%20showed%20moderate%202%2C2-diphenyl-1-picrylhydrazyl%20%28DPPH%29%20free%20radical%20scavenging%20activity.%22%2C%22date%22%3A%222020%5C%2F08%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1080%5C%2F09168451.2020.1764838%22%2C%22ISSN%22%3A%220916-8451%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%2C%22X8P588WG%22%5D%2C%22dateModified%22%3A%222022-08-05T16%3A14%3A02Z%22%7D%7D%2C%7B%22key%22%3A%22GJ6BITWF%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Wold%20et%20al.%22%2C%22parsedDate%22%3A%222020-08%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EWold%2C%20C.%20W.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20Wangensteen%2C%20H.%2C%20%26amp%3B%20Inngjerdingen%2C%20K.%20T.%20%282020%29.%20Bioactive%20triterpenoids%20and%20water-soluble%20melanin%20from%20Inonotus%20obliquus%20%28Chaga%29%20with%20immunomodulatory%20activity.%20%3Ci%3EJournal%20of%20Functional%20Foods%3C%5C%2Fi%3E%2C%20%3Ci%3E71%3C%5C%2Fi%3E.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.jff.2020.104025%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.jff.2020.104025%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Bioactive%20triterpenoids%20and%20water-soluble%20melanin%20from%20Inonotus%20obliquus%20%28Chaga%29%20with%20immunomodulatory%20activity%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20W.%22%2C%22lastName%22%3A%22Wold%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%22%2C%22lastName%22%3A%22Wangensteen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%20T.%22%2C%22lastName%22%3A%22Inngjerdingen%22%7D%5D%2C%22abstractNote%22%3A%22The%20fungus%20Inonotus%20obliquus%20has%20historically%20been%20used%20in%20traditional%20medicine%20in%20Europe%20and%20Asia.%20A%20melanin%20fraction%20and%20six%20triterpenoids%20were%20obtained%20from%20I.%20obliquus%20sclerotia%2C%20and%20evaluated%20in%20various%20bioassays%20including%20for%20immunomodulatory%2C%20cytotoxicity%20and%20enzyme-interacting%20properties.%20The%20water-soluble%2C%20nitrogenfree%20melanin%20fraction%20and%20the%20triterpenoids%20beta%203-hydroxy-8%2C24-dien-21-al%20%281%29%20and%20inotodiol%20%282%29%20displayed%20potent%20activity%20in%20a%20human%20complement%20assay.%20The%20melanin%20fraction%20inhibited%20the%20complement%20cascade%2C%20whereas%201%20and%202%20activated%20the%20same%20cascade.%20Compound%202%2C%20as%20well%20as%20betulinic%20acid%20%283%29%20and%20betulin%20%284%29%20had%20anti-proliferative%20properties%20against%20the%20colon%20adenocarcinoma%20cell%20line%20HT29-MTX.%20Further%2C%20the%20melanin%20fraction%20and%20betulin-3-O-caffeate%20%286%29%20reduced%20nitric%20oxide%20production%20in%20primary%20murine%20macrophages.%20Furthermore%2C%20the%20metabolites%20were%20nontoxic%20against%20the%20common%20gut%20bacteria%20E.%20coll.%20and%20B.%20subtilis.%20The%20results%20demonstrate%20the%20anti-inflammatory%20and%20immunomodulatory%20effects%20of%20I.%20obliquus%20melanin%20and%20triterpenoids%2C%20which%20could%20potentially%20justify%20the%20consumption%20of%20this%20increasingly%20popular%20%5C%22edible%5C%22%20fungus.%22%2C%22date%22%3A%222020%5C%2F08%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.jff.2020.104025%22%2C%22ISSN%22%3A%221756-4646%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A24Z%22%7D%7D%2C%7B%22key%22%3A%22ZRBBCAZK%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ndukwe%20et%20al.%22%2C%22parsedDate%22%3A%222020-07%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ENdukwe%2C%20I.%20E.%2C%20Wang%2C%20X.%2C%20Lam%2C%20N.%20Y.%20S.%2C%20Ermanis%2C%20K.%2C%20Alexander%2C%20K.%20L.%2C%20Bertin%2C%20M.%20J.%2C%20Martin%2C%20G.%20E.%2C%20Muir%2C%20G.%2C%20Paterson%2C%20I.%2C%20Britton%2C%20R.%2C%20Goodman%2C%20J.%20M.%2C%20Helfrich%2C%20E.%20J.%20N.%2C%20Piel%2C%20J.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Williamson%2C%20R.%20T.%20%282020%29.%20Synergism%20of%20anisotropic%20and%20computational%20NMR%20methods%20reveals%20the%20likely%20configuration%20of%20phormidolide%20A.%20%3Ci%3EChemical%20Communications%3C%5C%2Fi%3E%2C%20%3Ci%3E56%3C%5C%2Fi%3E%2855%29%2C%207565%26%23x2013%3B7568.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1039%5C%2Fd0cc03055d%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1039%5C%2Fd0cc03055d%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Synergism%20of%20anisotropic%20and%20computational%20NMR%20methods%20reveals%20the%20likely%20configuration%20of%20phormidolide%20A%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22I.%20E.%22%2C%22lastName%22%3A%22Ndukwe%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22X.%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22N.%20Y.%20S.%22%2C%22lastName%22%3A%22Lam%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%22%2C%22lastName%22%3A%22Ermanis%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%20L.%22%2C%22lastName%22%3A%22Alexander%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20J.%22%2C%22lastName%22%3A%22Bertin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%20E.%22%2C%22lastName%22%3A%22Martin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%22%2C%22lastName%22%3A%22Muir%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22I.%22%2C%22lastName%22%3A%22Paterson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Britton%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20M.%22%2C%22lastName%22%3A%22Goodman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%20J.%20N.%22%2C%22lastName%22%3A%22Helfrich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Piel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%20T.%22%2C%22lastName%22%3A%22Williamson%22%7D%5D%2C%22abstractNote%22%3A%22Characterization%20of%20the%20complex%20molecular%20scaffold%20of%20the%20marine%20polyketide%20natural%20product%20phormidolide%20A%20represents%20a%20challenge%20that%20has%20persisted%20for%20nearly%20two%20decades.%20In%20light%20of%20discordant%20results%20arising%20from%20recent%20synthetic%20and%20biosynthetic%20reports%2C%20a%20rigorous%20study%20of%20the%20configuration%20of%20phormidolide%20A%20was%20necessary.%20This%20report%20outlines%20a%20synergistic%20effort%20employing%20computational%20and%20anisotropic%20NMR%20investigation%2C%20that%20provided%20orthogonal%20confirmation%20of%20the%20reassigned%20side%20chain%2C%20as%20well%20as%20supporting%20a%20further%20correction%20of%20the%20C7%20stereocenter.%22%2C%22date%22%3A%222020%5C%2F07%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1039%5C%2Fd0cc03055d%22%2C%22ISSN%22%3A%221359-7345%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A46Z%22%7D%7D%2C%7B%22key%22%3A%22BN59F7V2%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Sequeira%20et%20al.%22%2C%22parsedDate%22%3A%222020-07%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ESequeira%2C%20E.%2C%20Pierce%2C%20M.%20L.%2C%20Akasheh%2C%20D.%2C%20Sellers%2C%20S.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20Baden%2C%20D.%20G.%2C%20%26amp%3B%20Murray%2C%20T.%20F.%20%282020%29.%20Epicortical%20Brevetoxin%20Treatment%20Promotes%20Neural%20Repair%20and%20Functional%20Recovery%20after%20Ischemic%20Stroke.%20%3Ci%3EMarine%20Drugs%3C%5C%2Fi%3E%2C%20%3Ci%3E18%3C%5C%2Fi%3E%287%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmd18070374%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmd18070374%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Epicortical%20Brevetoxin%20Treatment%20Promotes%20Neural%20Repair%20and%20Functional%20Recovery%20after%20Ischemic%20Stroke%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Sequeira%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20L.%22%2C%22lastName%22%3A%22Pierce%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%22%2C%22lastName%22%3A%22Akasheh%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Sellers%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%20G.%22%2C%22lastName%22%3A%22Baden%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%20F.%22%2C%22lastName%22%3A%22Murray%22%7D%5D%2C%22abstractNote%22%3A%22Emerging%20literature%20suggests%20that%20after%20a%20stroke%2C%20the%20peri-infarct%20region%20exhibits%20dynamic%20changes%20in%20excitability.%20In%20rodent%20stroke%20models%2C%20treatments%20that%20enhance%20excitability%20in%20the%20peri-infarct%20cerebral%20cortex%20promote%20motor%20recovery.%20This%20increase%20in%20cortical%20excitability%20and%20plasticity%20is%20opposed%20by%20increases%20in%20tonic%20GABAergic%20inhibition%20in%20the%20peri-infarct%20zone%20beginning%20three%20days%20after%20a%20stroke%20in%20a%20mouse%20model.%20Maintenance%20of%20a%20favorable%20excitatory-inhibitory%20balance%20promoting%20cerebrocortical%20excitability%20could%20potentially%20improve%20recovery.%20Brevetoxin-2%20%28PbTx-2%29%20is%20a%20voltage-gated%20sodium%20channel%20%28VGSC%29%20gating%20modifier%20that%20increases%20intracellular%20sodium%20%28%5BNa%2B%5Di%29%2C%20upregulates%20N-methyl-D-aspartate%20receptor%20%28NMDAR%29%20channel%20activity%20and%20engages%20downstream%20calcium%20%28Ca2%2B%29%20signaling%20pathways.%20In%20immature%20cerebrocortical%20neurons%2C%20PbTx-2%20promoted%20neuronal%20structural%20plasticity%20by%20increasing%20neurite%20outgrowth%2C%20dendritogenesis%20and%20synaptogenesis.%20We%20hypothesized%20that%20PbTx-2%20may%20promote%20excitability%20and%20structural%20remodeling%20in%20the%20peri-infarct%20region%2C%20leading%20to%20improved%20functional%20outcomes%20following%20a%20stroke.%20We%20tested%20this%20hypothesis%20using%20epicortical%20application%20of%20PbTx-2%20after%20a%20photothrombotic%20stroke%20in%20mice.%20We%20show%20that%20PbTx-2%20enhanced%20the%20dendritic%20arborization%20and%20synapse%20density%20of%20cortical%20layer%20V%20pyramidal%20neurons%20in%20the%20peri-infarct%20cortex.%20PbTx-2%20also%20produced%20a%20robust%20improvement%20of%20motor%20recovery.%20These%20results%20suggest%20a%20novel%20pharmacologic%20approach%20to%20mimic%20activity-dependent%20recovery%20from%20stroke.%22%2C%22date%22%3A%222020%5C%2F07%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3390%5C%2Fmd18070374%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A31Z%22%7D%7D%2C%7B%22key%22%3A%22SV9R9KHV%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Keller%20et%20al.%22%2C%22parsedDate%22%3A%222020-04%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EKeller%2C%20L.%2C%20Siqueira-Neto%2C%20J.%20L.%2C%20Souza%2C%20J.%20M.%2C%20Eribez%2C%20K.%2C%20LaMonte%2C%20G.%20M.%2C%20Smith%2C%20J.%20E.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282020%29.%20Palstimolide%20A%3A%20A%20complex%20polyhydroxy%20macrolide%20with%20antiparasitic%20activity.%20%3Ci%3EMolecules%3C%5C%2Fi%3E%2C%20%3Ci%3E25%3C%5C%2Fi%3E%287%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmolecules25071604%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.3390%5C%2Fmolecules25071604%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Palstimolide%20A%3A%20A%20complex%20polyhydroxy%20macrolide%20with%20antiparasitic%20activity%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Keller%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20L.%22%2C%22lastName%22%3A%22Siqueira-Neto%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20M.%22%2C%22lastName%22%3A%22Souza%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%22%2C%22lastName%22%3A%22Eribez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%20M.%22%2C%22lastName%22%3A%22LaMonte%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20E.%22%2C%22lastName%22%3A%22Smith%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22Marine%20Cyanobacteria%20%28blue-green%20algae%29%20have%20been%20shown%20to%20possess%20an%20enormous%20potential%20to%20produce%20structurally%20diverse%20natural%20products%20that%20exhibit%20a%20broad%20spectrum%20of%20potent%20biological%20activities%2C%20including%20cytotoxic%2C%20antifungal%2C%20antiparasitic%2C%20antiviral%2C%20and%20antibacterial%20activities.%20Here%2C%20we%20report%20the%20isolation%20and%20structure%20determination%20of%20palstimolide%20A%2C%20a%20complex%20polyhydroxy%20macrolide%20with%20a%2040-membered%20ring%20that%20was%20isolated%20from%20a%20tropical%20marine%20cyanobacterium%20collected%20at%20Palmyra%20Atoll.%20NMR-guided%20fractionation%20in%20combination%20with%20MS2-based%20molecular%20networking%20and%20isolation%20via%20HPLC%20yielded%200.7%20mg%20of%20the%20pure%20compound.%20The%20small%20quantity%20isolated%20along%20with%20the%20presence%20of%20significant%20signal%20degeneracy%20in%20both%20the%20H-1%20and%20C-13-NMR%20spectra%20complicated%20the%20structure%20elucidation%20of%20palstimolide%20A.%20Various%20NMR%20experiments%20and%20solvent%20systems%20were%20employed%2C%20including%20the%20LR-HSQMBC%20experiment%20that%20allows%20the%20detection%20of%20long-range%20H-1-C-13%20correlation%20data%20across%204-%2C%205-%2C%20and%20even%206-bonds.%20This%20expanded%20NMR%20data%20set%20enabled%20the%20elucidation%20of%20the%20palstimolide%27s%20planar%20structure%2C%20which%20is%20characterized%20by%20several%201%2C5-disposed%20hydroxy%20groups%20as%20well%20as%20a%20tert-butyl%20group.%20The%20compound%20showed%20potent%20antimalarial%20activity%20with%20an%20IC50%20of%20223%20nM%20as%20well%20as%20interesting%20anti-leishmanial%20activity%20with%20an%20IC50%20of%204.67%20mu%20M.%22%2C%22date%22%3A%222020%5C%2F04%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.3390%5C%2Fmolecules25071604%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A41Z%22%7D%7D%2C%7B%22key%22%3A%22QDCGRR93%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Li%20et%20al.%22%2C%22parsedDate%22%3A%222020-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELi%2C%20Y.%20Y.%2C%20Yu%2C%20H.%20B.%2C%20Zhang%2C%20Y.%2C%20Leao%2C%20T.%2C%20Glukhov%2C%20E.%2C%20Pierce%2C%20M.%20L.%2C%20Zhang%2C%20C.%2C%20Kim%2C%20H.%2C%20Mao%2C%20H.%20H.%2C%20Fang%2C%20F.%2C%20Cottrell%2C%20G.%20W.%2C%20Murray%2C%20T.%20F.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20L.%2C%20Guan%2C%20H.%20S.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282020%29.%20Pagoamide%20A%2C%20a%20cyclic%20depsipeptide%20isolated%20from%20a%20cultured%20marine%20chlorophyte%2C%20Derbesia%20sp.%2C%20using%20MS%5C%2FMS-based%20molecular%20networking.%20%3Ci%3EJournal%20of%20Natural%20Products%3C%5C%2Fi%3E%2C%20%3Ci%3E83%3C%5C%2Fi%3E%283%29%2C%20617%26%23x2013%3B625.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.9b01019%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jnatprod.9b01019%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Pagoamide%20A%2C%20a%20cyclic%20depsipeptide%20isolated%20from%20a%20cultured%20marine%20chlorophyte%2C%20Derbesia%20sp.%2C%20using%20MS%5C%2FMS-based%20molecular%20networking%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%20Y.%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%20B.%22%2C%22lastName%22%3A%22Yu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%22%2C%22lastName%22%3A%22Leao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20L.%22%2C%22lastName%22%3A%22Pierce%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%20H.%22%2C%22lastName%22%3A%22Mao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22F.%22%2C%22lastName%22%3A%22Fang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%20W.%22%2C%22lastName%22%3A%22Cottrell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%20F.%22%2C%22lastName%22%3A%22Murray%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%20S.%22%2C%22lastName%22%3A%22Guan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22A%20thiazole-containing%20cyclic%20depsipeptide%20with%2011%20amino%20acid%20residues%2C%20named%20pagoamide%20A%20%281%29%2C%20was%20isolated%20from%20laboratory%20cultures%20of%20a%20marine%20Chlorophyte%2C%20Derbesia%20sp.%20This%20green%20algal%20sample%20was%20collected%20from%20America%20Samoa%2C%20and%20pagoamide%20A%20was%20isolated%20using%20guidance%20by%20MS%5C%2FMS-based%20molecular%20networking.%20Cultures%20were%20grown%20in%20a%20light-%20and%20temperature-controlled%20environment%20and%20harvested%20after%20several%20months%20of%20growth.%20The%20planar%20structure%20of%20pagoamide%20A%20%281%29%20was%20characterized%20by%20detailed%201D%20and%202D%20NMR%20experiments%20along%20with%20MS%20and%20UV%20analysis.%20The%20absolute%20configurations%20of%20its%20amino%20acid%20residues%20were%20determined%20by%20advanced%20Marfey%27s%20analysis%20following%20chemical%20hydrolysis%20and%20hydrazinolysis%20reactions.%20Two%20of%20the%20residues%20in%20pagoamide%20A%20%281%29%2C%20phenylalanine%20and%20serine%2C%20each%20occurred%20twice%20in%20the%20molecule%2C%20once%20in%20the%20D-%20and%20once%20in%20the%20L-configuration.%20The%20biosynthetic%20origin%20of%20pagoamide%20A%20%281%29%20was%20considered%20in%20light%20of%20other%20natural%20products%20investigations%20with%20coenocytic%20green%20algae.%22%2C%22date%22%3A%222020%5C%2F03%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.jnatprod.9b01019%22%2C%22ISSN%22%3A%220163-3864%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%2C%22X8P588WG%22%5D%2C%22dateModified%22%3A%222022-08-05T16%3A17%3A08Z%22%7D%7D%2C%7B%22key%22%3A%22HCFSTKU5%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Keller%20et%20al.%22%2C%22parsedDate%22%3A%222020-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EKeller%2C%20L.%2C%20Canuto%2C%20K.%20M.%2C%20Liu%2C%20C.%20X.%2C%20Suzuki%2C%20B.%20M.%2C%20Almaliti%2C%20J.%2C%20Sikandar%2C%20A.%2C%20Naman%2C%20C.%20B.%2C%20Glukhov%2C%20E.%2C%20Luo%2C%20D.%20M.%2C%20Duggan%2C%20B.%20M.%2C%20Luesch%2C%20H.%2C%20Koehnke%2C%20J.%2C%20O%26%23x2019%3BDonoghue%2C%20A.%20J.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282020%29.%20Tutuilamides%20A-C%3A%20Vinyl-chloride-containing%20cyclodepsipeptides%20from%20marine%20cyanobacteria%20with%20potent%20elastase%20inhibitory%20properties.%20%3Ci%3EAcs%20Chemical%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E15%3C%5C%2Fi%3E%283%29%2C%20751%26%23x2013%3B757.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facschembio.9b00992%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facschembio.9b00992%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Tutuilamides%20A-C%3A%20Vinyl-chloride-containing%20cyclodepsipeptides%20from%20marine%20cyanobacteria%20with%20potent%20elastase%20inhibitory%20properties%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Keller%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%20M.%22%2C%22lastName%22%3A%22Canuto%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20X.%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%20M.%22%2C%22lastName%22%3A%22Suzuki%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Almaliti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Sikandar%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20B.%22%2C%22lastName%22%3A%22Naman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%20M.%22%2C%22lastName%22%3A%22Luo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%20M.%22%2C%22lastName%22%3A%22Duggan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%22%2C%22lastName%22%3A%22Luesch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Koehnke%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22O%27Donoghue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22Marine%20cyanobacteria%20%28blue-green%20algae%29%20have%20been%20shown%20to%20possess%20an%20enormous%20capacity%20to%20produce%20structurally%20diverse%20natural%20products%20that%20exhibit%20a%20broad%20spectrum%20of%20potent%20biological%20activities%2C%20including%20cytotoxic%2C%20antifungal%2C%20antiparasitic%2C%20antiviral%2C%20and%20antibacterial%20activities.%20Using%20mass-spectrometryguided%20fractionation%20together%20with%20molecular%20networking%2C%20cyanobacterial%20field%20collections%20from%20American%20Samoa%20and%20Palmyra%20Atoll%20yielded%20three%20new%20cyclic%20peptides%2C%20tutuilamides%20A-C.%20Their%20structures%20were%20established%20by%20spectroscopic%20techniques%20including%201D%20and%202D%20NMR%2C%20HR-MS%2C%20and%20chemical%20derivatization.%20Structure%20elucidation%20was%20facilitated%20by%20employing%20advanced%20NMR%20techniques%20including%20nonuniform%20sampling%20in%20combination%20with%20the%201%2C1-ADEQUATE%20experiment.%20These%20cyclic%20peptides%20are%20characterized%20by%20the%20presence%20of%20several%20unusual%20residues%20including%203-amino-6-hydroxy-2-piperidone%20and%202-amino-2-butenoic%20acid%2C%20together%20with%20a%20novel%20vinyl%20chloride-containing%20residue.%20Tutuilamides%20A-C%20show%20potent%20elastase%20inhibitory%20activity%20together%20with%20moderate%20potency%20in%20H-460%20lung%20cancer%20cell%20cytotoxicity%20assays.%20The%20binding%20mode%20to%20elastase%20was%20analyzed%20by%20X-ray%20crystallography%20revealing%20a%20reversible%20binding%20mode%20similar%20to%20the%20natural%20product%20lyngbyastatin%207.%20The%20presence%20of%20an%20additional%20hydrogen%20bond%20with%20the%20amino%20acid%20backbone%20of%20the%20flexible%20side%20chain%20of%20tutuilamide%20A%2C%20compared%20to%20lyngbyastatin%207%2C%20facilitates%20its%20stabilization%20in%20the%20elastase%20binding%20pocket%20and%20possibly%20explains%20its%20enhanced%20inhibitory%20potency.%22%2C%22date%22%3A%222020%5C%2F03%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1021%5C%2Facschembio.9b00992%22%2C%22ISSN%22%3A%221554-8929%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A48Z%22%7D%7D%2C%7B%22key%22%3A%22YHUSUI9W%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Reher%20et%20al.%22%2C%22parsedDate%22%3A%222020-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EReher%2C%20R.%2C%20Kim%2C%20H.%20W.%2C%20Zhang%2C%20C.%2C%20Mao%2C%20H.%20H.%2C%20Wang%2C%20M.%20X.%2C%20Nothias%2C%20L.%20F.%2C%20Caraballo-Rodriguez%2C%20A.%20M.%2C%20Glukhov%2C%20E.%2C%20Teke%2C%20B.%2C%20Leao%2C%20T.%2C%20Alexander%2C%20K.%20L.%2C%20Duggan%2C%20B.%20M.%2C%20Van%20Everbroeck%2C%20E.%20L.%2C%20Dorrestein%2C%20P.%20C.%2C%20Cottrell%2C%20G.%20W.%2C%20%26amp%3B%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%20%282020%29.%20A%20convolutional%20neural%20network-based%20approach%20for%20the%20rapid%20annotation%20of%20molecularly%20diverse%20natural%20products.%20%3Ci%3EJournal%20of%20the%20American%20Chemical%20Society%3C%5C%2Fi%3E%2C%20%3Ci%3E142%3C%5C%2Fi%3E%289%29%2C%204114%26%23x2013%3B4120.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Fjacs.9b13786%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Fjacs.9b13786%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22A%20convolutional%20neural%20network-based%20approach%20for%20the%20rapid%20annotation%20of%20molecularly%20diverse%20natural%20products%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Reher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%20W.%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%20H.%22%2C%22lastName%22%3A%22Mao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20X.%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%20F.%22%2C%22lastName%22%3A%22Nothias%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20M.%22%2C%22lastName%22%3A%22Caraballo-Rodriguez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%22%2C%22lastName%22%3A%22Teke%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%22%2C%22lastName%22%3A%22Leao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%20L.%22%2C%22lastName%22%3A%22Alexander%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%20M.%22%2C%22lastName%22%3A%22Duggan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%20L.%22%2C%22lastName%22%3A%22Van%20Everbroeck%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%20C.%22%2C%22lastName%22%3A%22Dorrestein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%20W.%22%2C%22lastName%22%3A%22Cottrell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%5D%2C%22abstractNote%22%3A%22This%20report%20describes%20the%20first%20application%20of%20the%20novel%20NMR-based%20machine%20learning%20tool%20%5C%22Small%20Molecule%20Accurate%20Recognition%20Technology%5C%22%20%28SMART%202.0%29%20for%20mixture%20analysis%20and%20subsequent%20accelerated%20discovery%20and%20characterization%20of%20new%20natural%20products.%20The%20concept%20was%20applied%20to%20the%20extract%20of%20a%20filamentous%20marine%20cyanobacterium%20known%20to%20be%20a%20prolific%20producer%20of%20cytotoxic%20natural%20products.%20This%20environmental%20Symploca%20extract%20was%20roughly%20fractionated%2C%20and%20then%20prioritized%20and%20guided%20by%20cancer%20cell%20cytotoxicity%2C%20NMR-based%20SMART%202.0%2C%20and%20MS2-based%20molecular%20networking.%20This%20led%20to%20the%20isolation%20and%20rapid%20identification%20of%20a%20new%20chimeric%20swinholide-like%20macrolide%2C%20symplocolide%20A%2C%20as%20well%20as%20the%20annotation%20of%20swinholide%20A%2C%20samholides%20A-I%2C%20and%20several%20new%20derivatives.%20The%20planar%20structure%20of%20symplocolide%20A%20was%20confirmed%20to%20be%20a%20structural%20hybrid%20between%20swinholide%20A%20and%20luminaolide%20B%20by%201D%5C%2F2D%20NMR%20and%20LC-MS2%20analysis.%20A%20second%20example%20applies%20SMART%202.0%20to%20the%20characterization%20of%20structurally%20novel%20cyclic%20peptides%2C%20and%20compares%20this%20approach%20to%20the%20recently%20appearing%20%5C%22atomic%20sort%5C%22%20method.%20This%20study%20exemplifies%20the%20revolutionary%20potential%20of%20combined%20traditional%20and%20deep%20learning-assisted%20analytical%20approaches%20to%20overcome%20longstanding%20challenges%20in%20natural%20products%20drug%20discovery.%22%2C%22date%22%3A%222020%5C%2F03%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1021%5C%2Fjacs.9b13786%22%2C%22ISSN%22%3A%220002-7863%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A28Z%22%7D%7D%2C%7B%22key%22%3A%22B4UFB9PK%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Uranga%20et%20al.%22%2C%22parsedDate%22%3A%222020-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EUranga%2C%20C.%20C.%2C%20Arroyo%2C%20P.%2C%20Duggan%2C%20B.%20M.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Edlunda%2C%20A.%20%282020%29.%20Commensal%20oral%20rothia%20mucilaginosa%20produces%20enterobactin%2C%20a%20metal-chelating%20siderophore.%20%3Ci%3EMSystems%3C%5C%2Fi%3E%2C%20%3Ci%3E5%3C%5C%2Fi%3E%282%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2FmSystems.00161-20%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2FmSystems.00161-20%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Commensal%20oral%20rothia%20mucilaginosa%20produces%20enterobactin%2C%20a%20metal-chelating%20siderophore%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20C.%22%2C%22lastName%22%3A%22Uranga%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%22%2C%22lastName%22%3A%22Arroyo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%20M.%22%2C%22lastName%22%3A%22Duggan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Edlunda%22%7D%5D%2C%22abstractNote%22%3A%22Next-generation%20sequencing%20studies%20of%20saliva%20and%20dental%20plaque%20from%20subjects%20in%20both%20healthy%20and%20diseased%20states%20have%20identified%20bacteria%20belonging%20to%20the%20Rothia%20genus%20as%20ubiquitous%20members%20of%20the%20oral%20microbiota.%20To%20gain%20a%20deeper%20understanding%20of%20molecular%20mechanisms%20underlying%20the%20chemical%20ecology%20of%20this%20unexplored%20group%2C%20we%20applied%20a%20genome%20mining%20approach%20that%20targets%20functionally%20important%20biosynthetic%20gene%20clusters%20%28BGCs%29.%20All%2045%20genomes%20that%20were%20mined%2C%20representing%20Rothia%20mucilaginosa%2C%20Rothia%20dentocariosa%2C%20and%20Rothia%20aeria%2C%20harbored%20a%20catechol-siderophore-like%20BGC.%20To%20explore%20siderophore%20production%20further%2C%20we%20grew%20the%20previously%20characterized%20R.%20mucilaginosa%20ATCC%2025296%20in%20liquid%20cultures%2C%20amended%20with%20glycerol%2C%20which%20led%20to%20the%20identification%20of%20the%20archetype%20siderophore%20enterobactin%20by%20using%20tandem%20liquid%20chromatography-mass%20spectrometry%20%28LC-MS%5C%2FMS%29%2C%20high-performance%20liquid%20chromatography%20%28HPLC%29%2C%20and%20nuclear%20magnetic%20resonance%20%28NMR%29%20spectroscopy.%20Normally%20attributed%20to%20pathogenic%20gut%20bacteria%2C%20R.%20mucilaginosa%20is%20the%20first%20commensal%20oral%20bacterium%20found%20to%20produce%20enterobactin.%20Cocultivation%20studies%20including%20R.%20mucilaginosa%20or%20purified%20enterobactin%20revealed%20that%20enterobactin%20reduced%20growth%20of%20certain%20strains%20of%20cariogenic%20Streptococcus%20mutans%20and%20pathogenic%20strains%20of%20Staphylococcus%20aureus.%20Commensal%20oral%20bacteria%20were%20either%20unaffected%2C%20reduced%20in%20growth%2C%20or%20induced%20to%20grow%20adjacent%20to%20enterobactin-producing%20R.%20mucilaginosa%20or%20the%20pure%20compound.%20Taken%20together%20with%20Rothia%27s%20known%20capacity%20to%20ferment%20a%20variety%20of%20carbohydrates%20and%20amino%20acids%2C%20our%20findings%20of%20enterobactin%20production%20add%20an%20additional%20level%20of%20explanation%20to%20R.%20mucilaginosa%27s%20prevalence%20in%20the%20oral%20cavity.%20Enterobactin%20is%20the%20strongest%20Fe%28III%29%20binding%20siderophore%20known%2C%20and%20its%20role%20in%20oral%20health%20requires%20further%20investigation.%20IMPORTANCE%20The%20communication%20language%20of%20the%20human%20oral%20microbiota%20is%20vastly%20underexplored.%20However%2C%20a%20few%20studies%20have%20shown%20that%20specialized%20small%20molecules%20encoded%20by%20BGCs%20have%20critical%20roles%20such%20as%20in%20colonization%20resistance%20against%20pathogens%20and%20quorum%20sensing.%20Here%2C%20by%20using%20a%20genome%20mining%20approach%20in%20combination%20with%20compound%20screening%20of%20growth%20cultures%2C%20we%20identified%20that%20the%20commensal%20oral%20community%20member%20R.%20mucilaginosa%20harbors%20a%20catecholate-siderophore%20BGC%2C%20which%20is%20responsible%20for%20the%20biosynthesis%20of%20enterobactin.%20The%20iron-scavenging%20role%20of%20enterobactin%20is%20known%20to%20have%20positive%20effects%20on%20the%20host%27s%20iron%20pool%20and%20negative%20effects%20on%20host%20immune%20function%3B%20however%2C%20its%20role%20in%20oral%20health%20remains%20unexplored.%20R.%20mucilaginosa%20was%20previously%20identified%20as%20an%20abundant%20community%20member%20in%20cystic%20fibrosis%2C%20where%20bacterial%20iron%20cycling%20plays%20a%20major%20role%20in%20virulence%20development.%20With%20respect%20to%20iron%27s%20broad%20biological%20importance%2C%20ironchelating%20enterobactin%20may%20explain%20R.%20mucilaginosa%27s%20colonization%20success%20in%20both%20health%20and%20disease.%22%2C%22date%22%3A%222020%5C%2F03%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1128%5C%2FmSystems.00161-20%22%2C%22ISSN%22%3A%222379-5077%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A28Z%22%7D%7D%2C%7B%22key%22%3A%22EF4UTJY9%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Skiba%20et%20al.%22%2C%22parsedDate%22%3A%222020-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ESkiba%2C%20M.%20A.%2C%20Tran%2C%20C.%20L.%2C%20Dan%2C%20Q.%20Y.%2C%20Sikkema%2C%20A.%20P.%2C%20Klaver%2C%20Z.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20Sherman%2C%20D.%20H.%2C%20%26amp%3B%20Smith%2C%20J.%20L.%20%282020%29.%20Repurposing%20the%20GNAT%20fold%20in%20the%20initiation%20of%20polyketide%20biosynthesis.%20%3Ci%3EStructure%3C%5C%2Fi%3E%2C%20%3Ci%3E28%3C%5C%2Fi%3E%281%29%2C%2063-%2B.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.str.2019.11.004%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.str.2019.11.004%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Repurposing%20the%20GNAT%20fold%20in%20the%20initiation%20of%20polyketide%20biosynthesis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20A.%22%2C%22lastName%22%3A%22Skiba%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20L.%22%2C%22lastName%22%3A%22Tran%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Q.%20Y.%22%2C%22lastName%22%3A%22Dan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20P.%22%2C%22lastName%22%3A%22Sikkema%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Z.%22%2C%22lastName%22%3A%22Klaver%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%20H.%22%2C%22lastName%22%3A%22Sherman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20L.%22%2C%22lastName%22%3A%22Smith%22%7D%5D%2C%22abstractNote%22%3A%22Natural%20product%20biosynthetic%20pathways%20are%20replete%20with%20enzymes%20repurposed%20for%20new%20catalytic%20functions.%20In%20some%20modular%20polyketide%20synthase%20%28PKS%29%20pathways%2C%20a%20GCN5-related%20N-acetyltransferase%20%28GNAT%29-like%20enzyme%20with%20an%20additional%20decarboxylation%20function%20initiates%20biosynthesis.%20Here%2C%20we%20probe%20two%20PKS%20GNAT-like%20domains%20for%20the%20dual%20activities%20of%20S-acyl%20transfer%20from%20coenzyme%20A%20%28CoA%29%20to%20an%20acyl%20carrier%20protein%20%28ACP%29%20and%20decarboxylation.%20The%20GphF%20and%20CurA%20GNAT-like%20domains%20selectively%20decarboxylate%20substrates%20that%20yield%20the%20anticipated%20pathway%20starter%20units.%20The%20GphF%20enzyme%20lacks%20detectable%20acyl%20transfer%20activity%2C%20and%20a%20crystal%20structure%20with%20an%20isobutyryl-CoA%20product%20analog%20reveals%20a%20partially%20occluded%20acyltransfer%20acceptor%20site.%20Further%20analysis%20indicates%20that%20the%20CurA%20GNAT-like%20domain%20also%20catalyzes%20only%20decarboxylation%2C%20and%20the%20initial%20acyl%20transfer%20is%20catalyzed%20by%20an%20unidentified%20enzyme.%20Thus%2C%20PKS%20GNAT-like%20domains%20are%20re-classified%20as%20GNAT-like%20decarboxylases.%20Two%20other%20decarboxylases%2C%20malonyl-CoA%20decarboxylase%20and%20EryM%2C%20reside%20on%20distant%20nodes%20of%20the%20superfamily%2C%20illustrating%20the%20adaptability%20of%20the%20GNAT%20fold.%22%2C%22date%22%3A%222020%5C%2F01%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.str.2019.11.004%22%2C%22ISSN%22%3A%220969-2126%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A43Z%22%7D%7D%2C%7B%22key%22%3A%22G82A4X5L%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Cao%20et%20al.%22%2C%22parsedDate%22%3A%222019-12%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ECao%2C%20L.%2C%20Gurevich%2C%20A.%2C%20Alexander%2C%20K.%20L.%2C%20Naman%2C%20C.%20B.%2C%20Leao%2C%20T.%2C%20Glukhov%2C%20E.%2C%20Luzzatto-Knaan%2C%20T.%2C%20Vargas%2C%20F.%2C%20Quinn%2C%20R.%2C%20Bouslimani%2C%20A.%2C%20Nothias%2C%20L.%20F.%2C%20Singh%2C%20N.%20K.%2C%20Sanders%2C%20J.%20G.%2C%20Benitez%2C%20R.%20A.%20S.%2C%20Thompson%2C%20L.%20R.%2C%20Hamid%2C%20M.%20N.%2C%20Morton%2C%20J.%20T.%2C%20Mikheenko%2C%20A.%2C%20Shlemov%2C%20A.%2C%20%26%23x2026%3B%20Mohimani%2C%20H.%20%282019%29.%20MetaMiner%3A%20A%20scalable%20peptidogenomics%20approach%20for%20discovery%20of%20ribosomal%20peptide%20natural%20products%20with%20blind%20modifications%20from%20microbial%20communities.%20%3Ci%3ECell%20Systems%3C%5C%2Fi%3E%2C%20%3Ci%3E9%3C%5C%2Fi%3E%286%29%2C%20600-%2B.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.cels.2019.09.004%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.cels.2019.09.004%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22MetaMiner%3A%20A%20scalable%20peptidogenomics%20approach%20for%20discovery%20of%20ribosomal%20peptide%20natural%20products%20with%20blind%20modifications%20from%20microbial%20communities%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Cao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Gurevich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%20L.%22%2C%22lastName%22%3A%22Alexander%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20B.%22%2C%22lastName%22%3A%22Naman%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%22%2C%22lastName%22%3A%22Leao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22E.%22%2C%22lastName%22%3A%22Glukhov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22T.%22%2C%22lastName%22%3A%22Luzzatto-Knaan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22F.%22%2C%22lastName%22%3A%22Vargas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Quinn%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Bouslimani%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%20F.%22%2C%22lastName%22%3A%22Nothias%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22N.%20K.%22%2C%22lastName%22%3A%22Singh%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20G.%22%2C%22lastName%22%3A%22Sanders%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%20A.%20S.%22%2C%22lastName%22%3A%22Benitez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%20R.%22%2C%22lastName%22%3A%22Thompson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%20N.%22%2C%22lastName%22%3A%22Hamid%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20T.%22%2C%22lastName%22%3A%22Morton%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Mikheenko%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Shlemov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%22%2C%22lastName%22%3A%22Korobeynikov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22I.%22%2C%22lastName%22%3A%22Friedberg%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22R.%22%2C%22lastName%22%3A%22Knight%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22K.%22%2C%22lastName%22%3A%22Venkateswaran%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%20C.%22%2C%22lastName%22%3A%22Dorrestein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22P.%20A.%22%2C%22lastName%22%3A%22Pevzner%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22H.%22%2C%22lastName%22%3A%22Mohimani%22%7D%5D%2C%22abstractNote%22%3A%22Ribosomally%20synthesized%20and%20post-translationally%20modified%20peptides%20%28RiPPs%29%20are%20an%20important%20class%20of%20natural%20products%20that%20contain%20antibiotics%20and%20a%20variety%20of%20other%20bioactive%20compounds.%20The%20existing%20methods%20for%20discovery%20of%20RiPPs%20by%20combining%20genome%20mining%20and%20computational%20mass%20spectrometry%20are%20limited%20to%20discovering%20specific%20classes%20of%20RiPPs%20from%20small%20datasets%2C%20and%20these%20methods%20fail%20to%20handle%20unknown%20post-translational%20modifications.%20Here%2C%20we%20present%20MetaMiner%2C%20a%20software%20tool%20for%20addressing%20these%20challenges%20that%20is%20compatible%20with%20large-scale%20screening%20platforms%20for%20natural%20product%20discovery.%20After%20searching%20millions%20of%20spectra%20in%20the%20Global%20Natural%20Products%20Social%20%28GNPS%29%20molecular%20networking%20infrastructure%20against%20just%20eight%20genomic%20and%20metagenomic%20datasets%2C%20MetaMiner%20discovered%2031%20known%20and%20seven%20unknown%20RiPPs%20from%20diverse%20microbial%20communities%2C%20including%20human%20microbiome%20and%20lichen%20microbiome%2C%20and%20microorganisms%20isolated%20from%20the%20International%20Space%20Station.%22%2C%22date%22%3A%222019%5C%2F12%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.cels.2019.09.004%22%2C%22ISSN%22%3A%222405-4712%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%2C%22X8P588WG%22%5D%2C%22dateModified%22%3A%222022-08-05T16%3A18%3A58Z%22%7D%7D%2C%7B%22key%22%3A%222CI3SPSN%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22O%27Donoghue%20et%20al.%22%2C%22parsedDate%22%3A%222019-11%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EO%26%23x2019%3BDonoghue%2C%20A.%20J.%2C%20Bibo-Verdugo%2C%20B.%2C%20Miyamoto%2C%20Y.%2C%20Wang%2C%20S.%20C.%2C%20Yang%2C%20J.%20Z.%2C%20Zuill%2C%20D.%20E.%2C%20Matsuka%2C%20S.%2C%20Jiang%2C%20Z.%20Z.%2C%20Almaliti%2C%20J.%2C%20Caffrey%2C%20C.%20R.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20%26amp%3B%20Eckmann%2C%20L.%20%282019%29.%2020S%20proteasome%20as%20a%20drug%20target%20in%20Trichomonas%20vaginalis.%20%3Ci%3EAntimicrobial%20Agents%20and%20Chemotherapy%3C%5C%2Fi%3E%2C%20%3Ci%3E63%3C%5C%2Fi%3E%2811%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2Faac.00448-19%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2Faac.00448-19%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%2220S%20proteasome%20as%20a%20drug%20target%20in%20Trichomonas%20vaginalis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22O%27Donoghue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%22%2C%22lastName%22%3A%22Bibo-Verdugo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Y.%22%2C%22lastName%22%3A%22Miyamoto%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%20C.%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%20Z.%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%20E.%22%2C%22lastName%22%3A%22Zuill%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%22%2C%22lastName%22%3A%22Matsuka%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Z.%20Z.%22%2C%22lastName%22%3A%22Jiang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Almaliti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20R.%22%2C%22lastName%22%3A%22Caffrey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22L.%22%2C%22lastName%22%3A%22Eckmann%22%7D%5D%2C%22abstractNote%22%3A%22Trichomoniasis%20is%20a%20sexually%20transmitted%20disease%20with%20hundreds%20of%20millions%20of%20annual%20cases%20worldwide.%20Approved%20treatment%20options%20are%20limited%20to%20two%20related%20nitro-heterocyclic%20compounds%2C%20yet%20resistance%20to%20these%20drugs%20is%20an%20increasing%20concern.%20New%20antimicrobials%20against%20the%20causative%20agent%2C%20Trichomonas%20vaginalis%2C%20are%20urgently%20needed.%20We%20show%20here%20that%20clinically%20approved%20anticancer%20drugs%20that%20inhibit%20the%20proteasome%2C%20a%20large%20protease%20complex%20with%20a%20critical%20role%20in%20degrading%20intracellular%20proteins%20in%20eukaryotes%2C%20have%20submicromolar%20activity%20against%20the%20parasite%20in%20vitro%20and%20on-target%20activity%20against%20the%20enriched%20T.%20vaginalis%20proteasome%20in%20cell-free%20assays.%20Proteomic%20analysis%20confirmed%20that%20the%20parasite%20has%20all%20seven%20alpha%20and%20seven%20beta%20subunits%20of%20the%20eukaryotic%20proteasome%20although%20they%20have%20only%20modest%20sequence%20identities%2C%20ranging%20from%2028%20to%2052%25%2C%20relative%20to%20the%20respective%20human%20proteasome%20subunits.%20A%20screen%20of%20proteasome%20inhibitors%20derived%20from%20a%20marine%20natural%20product%2C%20carmaphycin%2C%20revealed%20one%20derivative%2C%20carmaphycin-17%2C%20with%20greater%20activity%20against%20T.%20vaginalis%20than%20the%20reference%20drug%20metronidazole%2C%20the%20ability%20to%20overcome%20metronidazole%20resistance%2C%20and%20reduced%20human%20cytotoxicity%20compared%20to%20that%20of%20the%20anticancer%20proteasome%20inhibitors.%20The%20increased%20selectivity%20of%20carmaphycin-17%20for%20T.%20vaginalis%20was%20related%20to%20its%20%3E%205-fold%20greater%20potency%20against%20the%20beta%201%20and%20beta%205%20catalytic%20subunits%20of%20the%20T.%20vaginalis%20proteasome%20than%20against%20the%20human%20proteasome%20subunits.%20In%20a%20murine%20model%20of%20vaginal%20trichomonad%20infection%2C%20proteasome%20inhibitors%20eliminated%20or%20significantly%20reduced%20parasite%20burden%20upon%20topical%20treatment%20without%20any%20apparent%20adverse%20effects.%20Together%2C%20these%20findings%20validate%20the%20proteasome%20of%20T.%20vaginalis%20as%20a%20therapeutic%20target%20for%20development%20of%20a%20novel%20class%20of%20trichomonacidal%20agents.%22%2C%22date%22%3A%222019%5C%2F11%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1128%5C%2Faac.00448-19%22%2C%22ISSN%22%3A%220066-4804%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A21Z%22%7D%7D%2C%7B%22key%22%3A%22UNMAKYUC%22%2C%22library%22%3A%7B%22id%22%3A9129767%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Bibo-Verdugo%20et%20al.%22%2C%22parsedDate%22%3A%222019-10%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EBibo-Verdugo%2C%20B.%2C%20Wang%2C%20S.%20C.%2C%20Almaliti%2C%20J.%2C%20Ta%2C%20A.%20P.%2C%20Jiang%2C%20Z.%20Z.%2C%20Wong%2C%20D.%20A.%2C%20Lietz%2C%20C.%20B.%2C%20Suzuki%2C%20B.%20M.%2C%20El-Saldary%2C%20N.%2C%20Hook%2C%20V.%2C%20Salvesen%2C%20G.%20S.%2C%20%3Cstrong%3EGerwick%3C%5C%2Fstrong%3E%2C%20W.%20H.%2C%20Caffrey%2C%20C.%20R.%2C%20%26amp%3B%20O%26%23x2019%3BDonoghue%2C%20A.%20J.%20%282019%29.%20The%20proteasome%20as%20a%20drug%20target%20in%20the%20metazoan%20pathogen%2C%20Schistosoma%20mansoni.%20%3Ci%3EAcs%20Infectious%20Diseases%3C%5C%2Fi%3E%2C%20%3Ci%3E5%3C%5C%2Fi%3E%2810%29%2C%201802%26%23x2013%3B1812.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facsinfecdis.9b00237%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facsinfecdis.9b00237%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22The%20proteasome%20as%20a%20drug%20target%20in%20the%20metazoan%20pathogen%2C%20Schistosoma%20mansoni%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%22%2C%22lastName%22%3A%22Bibo-Verdugo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S.%20C.%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J.%22%2C%22lastName%22%3A%22Almaliti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20P.%22%2C%22lastName%22%3A%22Ta%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Z.%20Z.%22%2C%22lastName%22%3A%22Jiang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22D.%20A.%22%2C%22lastName%22%3A%22Wong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20B.%22%2C%22lastName%22%3A%22Lietz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%20M.%22%2C%22lastName%22%3A%22Suzuki%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22N.%22%2C%22lastName%22%3A%22El-Saldary%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22V.%22%2C%22lastName%22%3A%22Hook%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%20S.%22%2C%22lastName%22%3A%22Salvesen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22W.%20H.%22%2C%22lastName%22%3A%22Gerwick%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%20R.%22%2C%22lastName%22%3A%22Caffrey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22A.%20J.%22%2C%22lastName%22%3A%22O%27Donoghue%22%7D%5D%2C%22abstractNote%22%3A%22Proteases%20are%20fundamental%20to%20successful%20parasitism%2C%20including%20that%20of%20the%20schistosome%20flatworm%20parasite%2C%20which%20causes%20the%20disease%20schistosomiasis%20in%20200%20million%20people%20worldwide.%20The%20proteasome%20is%20receiving%20attention%20as%20a%20potential%20drug%20target%20for%20treatment%20of%20a%20variety%20of%20infectious%20parasitic%20diseases%2C%20but%20it%20has%20been%20understudied%20in%20the%20schistosome.%20Adult%20Schistosoma%20mansoni%20were%20incubated%20with%201%20mu%20M%20concentrations%20of%20the%20proteasome%20inhibitors%20bortezomib%2C%20carfilzomib%2C%20and%20MG132.%20After%2024%20h%2C%20bortezomib%20and%20carfilzomib%20decreased%20worm%20motility%20by%20more%20than%2085%25%20and%20endogenous%20proteasome%20activity%20by%20%3E75%25%2C%20and%20after%2072%20h%2C%20they%20increased%20caspase%20activity%20by%20%3E4.5-fold.%20The%20association%20between%20the%20engagement%20of%20the%20proteasome%20target%20and%20the%20phenotypic%20and%20biochemical%20effects%20recorded%20encouraged%20the%20chromatographic%20enrichment%20of%20the%20S.%20mansoni%20proteasome%20%28Sm20S%29.%20Activity%20assays%20with%20fluorogenic%20proteasome%20substrates%20revealed%20that%20Sm20S%20contains%20caspase-type%20%28beta%201%29%2C%20trypsin-type%20%28beta%202%29%2C%20and%20chymotrypsin-type%20%28beta%205%29%20activities.%20Sm20S%20was%20screened%20with%2011%20peptide%20epoxyketone%20inhibitors%20derived%20from%20the%20marine%20natural%20product%20carmaphycin%20B.%20Analogue%2017%20was%2027.4-fold%20less%20cytotoxic%20to%20HepG2%20cells%20than%20carmaphycin%20B%20and%20showed%20equal%20potency%20for%20the%20beta%205%20subunits%20of%20Sm20S%2C%20human%20constitutive%20proteasome%2C%20and%20human%20immunoproteasome.%20However%2C%20this%20analogue%20was%2013.2-fold%20more%20potent%20at%20targeting%20Sm20S%20beta%202%20than%20it%20was%20at%20targeting%20the%20equivalent%20subunits%20of%20the%20human%20enzymes.%20Furthermore%2C%201%20mu%20M%2017%20decreased%20both%20worm%20motility%20and%20endogenous%20Sm20S%20activity%20by%20more%20than%2090%25%20after%2024%20h.%20We%20provide%20direct%20evidence%20of%20the%20proteasome%27s%20importance%20to%20schistosome%20viability%20and%20identify%20a%20lead%20for%20which%20future%20studies%20will%20aim%20to%20improve%20the%20potency%2C%20selectivity%2C%20and%20safety.%22%2C%22date%22%3A%222019%5C%2F10%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1021%5C%2Facsinfecdis.9b00237%22%2C%22ISSN%22%3A%222373-8227%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%229BHAPH7Z%22%5D%2C%22dateModified%22%3A%222022-07-13T18%3A43%3A43Z%22%7D%7D%5D%7D
Lukowski, A. L., Hubert, F. M., Ngo, T.-E., Avalon, N. E., Gerwick, W. H., & Moore, B. S. (2023). Enzymatic Halogenation of Terminal Alkynes. Journal of the American Chemical Society, 145(34), 18716–18721. https://doi.org/10.1021/jacs.3c05750
Kim, H. W., Zhang, C., Reher, R., Wang, M., Alexander, K. L., Nothias, L.-F., Han, Y. K., Shin, H., Lee, K. Y., Lee, K. H., Kim, M. J., Dorrestein, P. C., Gerwick, W. H., & Cottrell, G. W. (2023). DeepSAT: Learning Molecular Structures from Nuclear Magnetic Resonance Data. Journal of Cheminformatics, 15(1), 71. https://doi.org/10.1186/s13321-023-00738-4
Boyarko, B., Podvin, S., Greenberg, B., Momper, J. D., Huang, Y., Gerwick, W. H., Bang, A. G., Quinti, L., Griciuc, A., Kim, D. Y., Tanzi, R. E., Feldman, H. H., & Hook, V. (2023). Evaluation of bumetanide as a potential therapeutic agent for Alzheimer’s disease. Frontiers in Pharmacology, 14, 1190402. https://doi.org/10.3389/fphar.2023.1190402
Almaliti, J., & Gerwick, W. H. (2023). Methods in marine natural product drug discovery: what’s new? Expert Opinion on Drug Discovery, 18(7), 687–691. https://doi.org/10.1080/17460441.2023.2214360
Almaliti, J., Fajtová, P., Calla, J., LaMonte, G. M., Feng, M., Rocamora, F., Ottilie, S., Glukhov, E., Boura, E., Suhandynata, R. T., Momper, J. D., Gilson, M. K., Winzeler, E. A., Gerwick, W. H., & O’Donoghue, A. J. (2023). Development of Potent and Highly Selective Epoxyketone‐Based Plasmodium Proteasome Inhibitors. Chemistry – A European Journal, 29(20), e202203958. https://doi.org/10.1002/chem.202203958
Shrestha, S. K., Min, K. H., Kim, S. W., Kim, H., Gerwick, W. H., & Soh, Y. (2023). Kalkitoxin: A Potent Suppressor of Distant Breast Cancer Metastasis. International Journal of Molecular Sciences, 24(2), 1207. https://doi.org/10.3390/ijms24021207
Mullowney, M. W., Duncan, K. R., Elsayed, S. S., Garg, N., Van Der Hooft, J. J. J., Martin, N. I., Meijer, D., Terlouw, B. R., Biermann, F., Blin, K., Durairaj, J., Gorostiola González, M., Helfrich, E. J. N., Huber, F., Leopold-Messer, S., Rajan, K., De Rond, T., Van Santen, J. A., Sorokina, M., … Medema, M. H. (2023). Artificial intelligence for natural product drug discovery. Nature Reviews Drug Discovery, 22(11), 895–916. https://doi.org/10.1038/s41573-023-00774-7
Deni, I., Stokes, B. H., Ward, K. E., Fairhurst, K. J., Pasaje, C. F. A., Yeo, T., Akbar, S., Park, H., Muir, R., Bick, D. S., Zhan, W., Zhang, H., Liu, Y. J., Ng, C. L., Kirkman, L. A., Almaliti, J., Gould, A. E., Duffey, M., O’Donoghue, A. J., … Fidock, D. A. (2023). Mitigating the risk of antimalarial resistance via covalent dual-subunit inhibition of the Plasmodium proteasome. Cell Chemical Biology, 30(5), 470-485.e6. https://doi.org/10.1016/j.chembiol.2023.03.002
Ternon, E., Thomas, O. P., Lemée, R., & Gerwick, W. H. (2022). Rapid Biotic and Abiotic Transformation of Toxins produced by Ostreopsis. cf. ovata. Marine Drugs, 20(12), 748. https://doi.org/10.3390/md20120748
Leão, T. F., Wang, M., da Silva, R., Gurevich, A., Bauermeister, A., Gomes, P. W. P., Brejnrod, A., Glukhov, E., Aron, A. T., Louwen, J. J. R., Kim, H. W., Reher, R., Fiore, M. F., van der Hooft, J. J. J., Gerwick, L., Gerwick, W. H., Bandeira, N., & Dorrestein, P. C. (2022). NPOmix: A machine learning classifier to connect mass spectrometry fragmentation data to biosynthetic gene clusters. PNAS Nexus, 1(5), pgac257. https://doi.org/10.1093/pnasnexus/pgac257
Reher, R., Aron, A. T., Fajtová, P., Stincone, P., Wagner, B., Pérez-Lorente, A. I., Liu, C., Shalom, I. Y. B., Bittremieux, W., Wang, M., Jeong, K., Matos-Hernandez, M. L., Alexander, K. L., Caro-Diaz, E. J., Naman, C. B., Scanlan, J. H. W., Hochban, P. M. M., Diederich, W. E., Molina-Santiago, C., … Petras, D. (2022). Native metabolomics identifies the rivulariapeptolide family of protease inhibitors. Nature Communications, 13(1), 4619. https://doi.org/10.1038/s41467-022-32016-6
Phan, V. V., Mosier, C., Yoon, M. C., Glukhov, E., Caffrey, C. R., O’Donoghue, A. J., Gerwick, W. H., & Hook, V. (2022). Discovery of pH-Selective Marine and Plant Natural Product Inhibitors of Cathepsin B Revealed by Screening at Acidic and Neutral pH Conditions. ACS Omega, 7(29), 25346–25352. https://doi.org/10.1021/acsomega.2c02287
Taton, A., Rohrer, S., Diaz, B., Reher, R., Caraballo Rodriguez, A. M., Pierce, M. L., Dorrestein, P. C., Gerwick, L., Gerwick, W. H., & Golden, J. W. (2022). Heterologous Expression in Anabaena of the Columbamide Pathway from the Cyanobacterium Moorena bouillonii and Production of New Analogs. ACS Chemical Biology, 17(7), 1910–1923. https://doi.org/10.1021/acschembio.2c00347
He, Y., Suyama, T. L., Kim, H., Glukhov, E., & Gerwick, W. H. (2022). Discovery of Novel Tyrosinase Inhibitors From Marine Cyanobacteria. Frontiers in Microbiology, 13, 912621. https://doi.org/10.3389/fmicb.2022.912621
Li, F.-L., Fu, V., Liu, G., Tang, T., Konradi, A. W., Peng, X., Kemper, E., Cravatt, B. F., Franklin, J. M., Wu, Z., Mayfield, J., Dixon, J. E., Gerwick, W. H., & Guan, K.-L. (2022). Hippo pathway regulation by phosphatidylinositol transfer protein and phosphoinositides. Nature Chemical Biology. https://doi.org/10.1038/s41589-022-01061-z
Wang, Y., Glukhov, E., He, Y. F., Liu, Y. Y., Zhou, L. J., Ma, X. X., Hu, X. Q., Hong, P. Z., Gerwick, W. H., & Zhang, Y. (2022). Secondary metabolite variation and bioactivities of two marine aspergillus strains in static co-culture investigated by molecular network analysis and multiple database mining based on LC-PDA-MS/MS. Antibiotics-Basel, 11(4), 26. https://doi.org/10.3390/antibiotics11040513
Da Silva, E. B., Sharma, V., Hernandez-Alvarez, L., Tang, A. H., Stoye, A., O’Donoghue, A. J., Gerwick, W. H., Payne, R. J., McKerrow, J. H., & Podust, L. M. (2022). Intramolecular interactions enhance the potency of gallinamide A analogues against Trypanosoma cruzi. Journal of Medicinal Chemistry, 65(5), 4255–4269. https://doi.org/10.1021/acs.jmedchem.1c02063
Mehrotra, S., Pierce, M. L., Cao, Z. Y., Jabba, S. V., Gerwick, W. H., & Murray, T. F. (2022). Antillatoxin-stimulated neurite outgrowth involves the brain-derived neurotrophic factor (BDNF)-tropomyosin related kinase B (TrkB) aignaling pathway br. Journal of Natural Products, 85(3), 562–571. https://doi.org/10.1021/acs.jnatprod.1c01001
Ashhurst, A. S., Tang, A. H., Fajtova, P., Yoon, M. C., Aggarwal, A., Bedding, M. J., Stoye, A., Beretta, L., Pwee, D., Drelich, A., Skinner, D., Li, L. F., Meek, T. D., McKerrow, J. H., Hook, V., Tseng, C. T., Larance, M., Turville, S., Gerwick, W. H., … Payne, R. J. (2022). Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L. Journal of Medicinal Chemistry, 65(4), 2956–2970. https://doi.org/10.1021/acs.jmedchem.1c01494
Yoon, M. C., Christy, M. P., Phan, V. V., Gerwick, W. H., Hook, G., O’Donoghue, A. J., & Hook, V. (2022). Molecular features of CA-074 pH-dependent inhibition of Cathepsin B. Biochemistry, 61(4), 228–238. https://doi.org/10.1021/acs.biochem.1c00684
Ottilie, S., Luth, M. R., Hellemann, E., Goldgof, G. M., Vigil, E., Kumar, P., Cheung, A. L., Song, M., Godinez-Macias, K. P., Carolino, K., Yang, J., Lopez, G., Abraham, M., Tarsio, M., LeBlanc, E., Whitesell, L., Schenken, J., Gunawan, F., Patel, R., … Winzeler, E. A. (2022). Adaptive laboratory evolution in S. cerevisiae highlights role of transcription factors in fungal xenobiotic resistance. Communications Biology, 5(1), 14. https://doi.org/10.1038/s42003-022-03076-7
Kim, G. J., Mascuch, S. J., Mevers, E., Boudreau, P. D., Gerwick, W. H., & Choi, H. (2022). Luquilloamides, cytotoxic lipopeptides from a puerto rican collection of the filamentous marine cyanobacterium Oscillatoria sp. Journal of Organic Chemistry, 13. https://doi.org/10.1021/acs.joc.1c02340
Kim, H. W., Zhang, C., Cottrell, G. W., & Gerwick, W. H. (2021). SMART-Miner: A convolutional neural network-based metabolite identification from H-1-C-13 HSQC spectra. Magnetic Resonance in Chemistry, 6. https://doi.org/10.1002/mrc.5240
Kim, H. W., Wang, M. X., Leber, C. A., Nothias, L. F., Reher, R., Kang, K. B., van der Hooft, J. J. J., Dorrestein, P. C., Gerwick, W. H., & Cottrell, G. W. (2021). NPClassifier: A Deep Neural Network-Based Structural Classification Tool for Natural Products. Journal of Natural Products, 84(11), 2795–2807. https://doi.org/10.1021/acs.jnatprod.1c00399
Almaliti, J., Fajtova, P., O’Donoghue, A. J., AlHindy, M., & Gerwick, W. H. (2021). Improved scalable synthesis of clinical candidate KZR-616, a selective immunoproteasome inhibitor. Chemistryselect, 6(44), 12461–12465. https://doi.org/10.1002/slct.202103455
Yoon, M. C., Solania, A., Jiang, Z. Z., Christy, M. P., Podvin, S., Mosier, C., Lietz, C. B., Ito, G., Gerwick, W. H., Wolan, D. W., Hook, G., O’Donoghue, A. J., & Hook, V. (2021). Selective neutral pH Inhibitor of Cathepsin B designed based on cleavage preferences at cytosolic and lysosomal pH conditions. Acs Chemical Biology, 16(9), 1628–1643. https://doi.org/10.1021/acschembio.1c00138
Iwasaki, A., Teranuma, K., Kurisawa, N., Rahmawati, Y., Jeelani, G., Nozaki, T., Gerwick, W. H., & Suenaga, K. (2021). First total synthesis and structure-activity relationship of iheyamide A, an antitrypanosomal linear peptide isolated from a Dapis sp. Marine cyanobacterium. Journal of Natural Products, 84(9), 2587–2593. https://doi.org/10.1021/acs.jnatprod.1c00792
Demirkiran, O., Almaliti, J., Leao, T., Navarro, G., Byrum, T., Valeriote, F. A., Gerwick, L., & Gerwick, W. H. (2021). Portobelamides A and B and Caciqueamide, Cytotoxic Peptidic Natural Products from a Caldora sp. Marine Cyanobacterium. Journal of Natural Products, 84(8), 2081–2093. https://doi.org/10.1021/acs.jnatprod.0c01383
Kim, H. W., Jeon, J. B., Zhang, M., Cho, H. M., Ryu, B., Lee, B. W., Gerwick, W. H., & Oh, W. K. (2021). SIRT1 Activation Enhancing 8,3 ’-Neolignans from the Twigs of Corylopsis coreana Uyeki. Plants-Basel, 10(8), 12. https://doi.org/10.3390/plants10081684
Taylor, K. S., Zhang, C., Glukhov, E., Gerwick, W. H., & Suyama, T. L. (2021). Total synthesis of laucysteinamide A, a monomeric congener of somocystinamide A. Journal of Natural Products, 84(3), 865–870. https://doi.org/10.1021/acs.jnatprod.0c01317
Li, L., Yang, M., Shrestha, S. K., Kim, H., Gerwick, W. H., & Soh, Y. (2021). Kalkitoxin reduces osteoclast formation and resorption and protects against inflammatory bone loss. International Journal of Molecular Sciences, 22(5). https://doi.org/10.3390/ijms22052303
Leber, C. A., Reyes, A. J., Biggs, J. S., & Gerwick, W. H. (2021). Cyanobacteria-shrimp colonies in the Mariana Islands. Aquatic Ecology. https://doi.org/10.1007/s10452-021-09837-6
Christy, M. P., Uekusa, Y., Gerwick, L., & Gerwick, W. H. (2021). Natural products with potential to treat RNA virus pathogens including SARS-CoV-2. Journal of Natural Products, 84(1), 161–182. https://doi.org/10.1021/acs.jnatprod.0c00968
Leao, T., Wang, M. X., Moss, N., da Silva, R., Sanders, J., Nurk, S., Gurevich, A., Humphrey, G., Reher, R., Zhu, Q. Y., Belda-Ferre, P., Glukhov, E., Whitner, S., Alexander, K. L., Rex, R., Pevzner, P., Dorrestein, P. C., Knight, R., Bandeira, N., … Gerwick, L. (2021). A multi-omics characterization of the natural product potential of tropical filamentous marine cyanobacteria. Marine Drugs, 19(1). https://doi.org/10.3390/md19010020
Taton, A., Ecker, A., Diaz, B., Moss, N. A., Anderson, B., Reher, R., Leao, T. F., Simkovsky, R., Dorrestein, P. C., Gerwick, L., Gerwick, W. H., & Golden, J. W. (2020). Heterologous expression of cryptomaldamide in a cyanobacterial host. Acs Synthetic Biology, 9(12), 3364–3376. https://doi.org/10.1021/acssynbio.0c00431
Li, Y. Y., Naman, C. B., Alexander, K. L., Guan, H. S., & Gerwick, W. H. (2020). The chemistry, biochemistry and pharmacology of marine natural products from Leptolyngbya, a chemically endowed genus of cyanobacteria. Marine Drugs, 18(10). https://doi.org/10.3390/md18100508
Leber, C. A., Naman, C. B., Keller, L., Almaliti, J., Caro-Diaz, E. J. E., Glukhov, E., Joseph, V., Sajeevan, T. P., Reyes, A. J., Biggs, J. S., Li, T., Yuan, Y., He, S., Yan, X. J., & Gerwick, W. H. (2020). Applying a chemogeographic strategy for natural product discovery from the marine cyanobacterium Moorena bouillonii. Marine Drugs, 18(10). https://doi.org/10.3390/md18100515
Yang, J. M., Liu, Y. Y., Yang, W. C., Ma, X. X., Nie, Y. Y., Glukhov, E., Gerwick, L., Gerwick, W. H., Lei, X. L., & Zhang, Y. (2020). An anti-inflammatory isoflavone from soybean inoculated with a marine fungusAspergillus terreusC23-3. Bioscience Biotechnology and Biochemistry, 84(8), 1546–1553. https://doi.org/10.1080/09168451.2020.1764838
Wold, C. W., Gerwick, W. H., Wangensteen, H., & Inngjerdingen, K. T. (2020). Bioactive triterpenoids and water-soluble melanin from Inonotus obliquus (Chaga) with immunomodulatory activity. Journal of Functional Foods, 71. https://doi.org/10.1016/j.jff.2020.104025
Ndukwe, I. E., Wang, X., Lam, N. Y. S., Ermanis, K., Alexander, K. L., Bertin, M. J., Martin, G. E., Muir, G., Paterson, I., Britton, R., Goodman, J. M., Helfrich, E. J. N., Piel, J., Gerwick, W. H., & Williamson, R. T. (2020). Synergism of anisotropic and computational NMR methods reveals the likely configuration of phormidolide A. Chemical Communications, 56(55), 7565–7568. https://doi.org/10.1039/d0cc03055d
Sequeira, E., Pierce, M. L., Akasheh, D., Sellers, S., Gerwick, W. H., Baden, D. G., & Murray, T. F. (2020). Epicortical Brevetoxin Treatment Promotes Neural Repair and Functional Recovery after Ischemic Stroke. Marine Drugs, 18(7). https://doi.org/10.3390/md18070374
Keller, L., Siqueira-Neto, J. L., Souza, J. M., Eribez, K., LaMonte, G. M., Smith, J. E., & Gerwick, W. H. (2020). Palstimolide A: A complex polyhydroxy macrolide with antiparasitic activity. Molecules, 25(7). https://doi.org/10.3390/molecules25071604
Li, Y. Y., Yu, H. B., Zhang, Y., Leao, T., Glukhov, E., Pierce, M. L., Zhang, C., Kim, H., Mao, H. H., Fang, F., Cottrell, G. W., Murray, T. F., Gerwick, L., Guan, H. S., & Gerwick, W. H. (2020). Pagoamide A, a cyclic depsipeptide isolated from a cultured marine chlorophyte, Derbesia sp., using MS/MS-based molecular networking. Journal of Natural Products, 83(3), 617–625. https://doi.org/10.1021/acs.jnatprod.9b01019
Keller, L., Canuto, K. M., Liu, C. X., Suzuki, B. M., Almaliti, J., Sikandar, A., Naman, C. B., Glukhov, E., Luo, D. M., Duggan, B. M., Luesch, H., Koehnke, J., O’Donoghue, A. J., & Gerwick, W. H. (2020). Tutuilamides A-C: Vinyl-chloride-containing cyclodepsipeptides from marine cyanobacteria with potent elastase inhibitory properties. Acs Chemical Biology, 15(3), 751–757. https://doi.org/10.1021/acschembio.9b00992
Reher, R., Kim, H. W., Zhang, C., Mao, H. H., Wang, M. X., Nothias, L. F., Caraballo-Rodriguez, A. M., Glukhov, E., Teke, B., Leao, T., Alexander, K. L., Duggan, B. M., Van Everbroeck, E. L., Dorrestein, P. C., Cottrell, G. W., & Gerwick, W. H. (2020). A convolutional neural network-based approach for the rapid annotation of molecularly diverse natural products. Journal of the American Chemical Society, 142(9), 4114–4120. https://doi.org/10.1021/jacs.9b13786
Uranga, C. C., Arroyo, P., Duggan, B. M., Gerwick, W. H., & Edlunda, A. (2020). Commensal oral rothia mucilaginosa produces enterobactin, a metal-chelating siderophore. MSystems, 5(2). https://doi.org/10.1128/mSystems.00161-20
Skiba, M. A., Tran, C. L., Dan, Q. Y., Sikkema, A. P., Klaver, Z., Gerwick, W. H., Sherman, D. H., & Smith, J. L. (2020). Repurposing the GNAT fold in the initiation of polyketide biosynthesis. Structure, 28(1), 63-+. https://doi.org/10.1016/j.str.2019.11.004
Cao, L., Gurevich, A., Alexander, K. L., Naman, C. B., Leao, T., Glukhov, E., Luzzatto-Knaan, T., Vargas, F., Quinn, R., Bouslimani, A., Nothias, L. F., Singh, N. K., Sanders, J. G., Benitez, R. A. S., Thompson, L. R., Hamid, M. N., Morton, J. T., Mikheenko, A., Shlemov, A., … Mohimani, H. (2019). MetaMiner: A scalable peptidogenomics approach for discovery of ribosomal peptide natural products with blind modifications from microbial communities. Cell Systems, 9(6), 600-+. https://doi.org/10.1016/j.cels.2019.09.004
O’Donoghue, A. J., Bibo-Verdugo, B., Miyamoto, Y., Wang, S. C., Yang, J. Z., Zuill, D. E., Matsuka, S., Jiang, Z. Z., Almaliti, J., Caffrey, C. R., Gerwick, W. H., & Eckmann, L. (2019). 20S proteasome as a drug target in Trichomonas vaginalis. Antimicrobial Agents and Chemotherapy, 63(11). https://doi.org/10.1128/aac.00448-19
Bibo-Verdugo, B., Wang, S. C., Almaliti, J., Ta, A. P., Jiang, Z. Z., Wong, D. A., Lietz, C. B., Suzuki, B. M., El-Saldary, N., Hook, V., Salvesen, G. S., Gerwick, W. H., Caffrey, C. R., & O’Donoghue, A. J. (2019). The proteasome as a drug target in the metazoan pathogen, Schistosoma mansoni. Acs Infectious Diseases, 5(10), 1802–1812. https://doi.org/10.1021/acsinfecdis.9b00237