Biosynthesis of Octacosamicin A: Uncommon Starter/extender Units and Product Releasing via Intermolecular Amidation
Octacosamicin A is an antifungal metabolite featuring a linear polyene‐polyol chain flanked by N‐hydroxyguanidine and glycine moieties. We report here that sub‐inhibitory concentrations of streptomycin elicited the production of octacosamicin A in Amycolatopsis azurea DSM 43854T. We identified the b...
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| Veröffentlicht in: | Chembiochem : a European journal of chemical biology 2024-01, Vol.25 (1), p.e202300590-n/a |
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| container_title | Chembiochem : a European journal of chemical biology |
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| creator | Liao, Yanghui Wang, Xue‐Jiao Ma, Guang‐Lei Candra, Hartono Qiu En, Sean Lee Khandelwal, Srashti Liang, Zhao‐Xun |
| description | Octacosamicin A is an antifungal metabolite featuring a linear polyene‐polyol chain flanked by N‐hydroxyguanidine and glycine moieties. We report here that sub‐inhibitory concentrations of streptomycin elicited the production of octacosamicin A in Amycolatopsis azurea DSM 43854T. We identified the biosynthetic gene cluster (oca BGC) that encodes a modular polyketide synthase (PKS) system for assembling the polyene‐polyol chain of octacosamicin A. Our analysis suggested that the N‐hydroxyguanidine unit originates from a 4‐guanidinobutyryl‐CoA starter unit, while the PKS incorporates an α‐hydroxyketone moiety using a (2R)‐hydroxymalonyl‐CoA extender unit. The modular PKS system contains a non‐canonical terminal module that lacks thioesterase (TE) and acyl carrier protein (ACP) domains, indicating the biosynthesis is likely to employ an unconventional and cryptic off‐loading mechanism that attaches glycine to the polyene‐polyol chain via an intermolecular amidation reaction.
The biosynthesis of octacosamicin A requires uncommon starter and extender units and likely employs an unusual mechanism for product release by catalysing an intermolecular amidation reaction. |
| doi_str_mv | 10.1002/cbic.202300590 |
| format | Article |
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The biosynthesis of octacosamicin A requires uncommon starter and extender units and likely employs an unusual mechanism for product release by catalysing an intermolecular amidation reaction.</description><identifier>ISSN: 1439-4227</identifier><identifier>EISSN: 1439-7633</identifier><identifier>DOI: 10.1002/cbic.202300590</identifier><identifier>PMID: 37908177</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Acyl carrier protein ; Biosynthesis ; biosynthetic gene cluster ; Fungicides ; Glycine ; guanidine ; ketosynthase ; Metabolites ; Modular systems ; Modular units ; Molecular chains ; Polyenes ; Polyketide synthase ; Polyketide Synthases - genetics ; Polyketide Synthases - metabolism ; Streptomycin</subject><ispartof>Chembiochem : a European journal of chemical biology, 2024-01, Vol.25 (1), p.e202300590-n/a</ispartof><rights>2023 Wiley‐VCH GmbH</rights><rights>2023 Wiley-VCH GmbH.</rights><rights>2024 Wiley‐VCH GmbH</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3820-40d871bc261e5a64f99fda54193c35338f0df0e16a664253ef1f6ca9e45c03993</cites><orcidid>0000-0002-3128-1330</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcbic.202300590$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcbic.202300590$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37908177$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liao, Yanghui</creatorcontrib><creatorcontrib>Wang, Xue‐Jiao</creatorcontrib><creatorcontrib>Ma, Guang‐Lei</creatorcontrib><creatorcontrib>Candra, Hartono</creatorcontrib><creatorcontrib>Qiu En, Sean Lee</creatorcontrib><creatorcontrib>Khandelwal, Srashti</creatorcontrib><creatorcontrib>Liang, Zhao‐Xun</creatorcontrib><title>Biosynthesis of Octacosamicin A: Uncommon Starter/extender Units and Product Releasing via Intermolecular Amidation</title><title>Chembiochem : a European journal of chemical biology</title><addtitle>Chembiochem</addtitle><description>Octacosamicin A is an antifungal metabolite featuring a linear polyene‐polyol chain flanked by N‐hydroxyguanidine and glycine moieties. We report here that sub‐inhibitory concentrations of streptomycin elicited the production of octacosamicin A in Amycolatopsis azurea DSM 43854T. We identified the biosynthetic gene cluster (oca BGC) that encodes a modular polyketide synthase (PKS) system for assembling the polyene‐polyol chain of octacosamicin A. Our analysis suggested that the N‐hydroxyguanidine unit originates from a 4‐guanidinobutyryl‐CoA starter unit, while the PKS incorporates an α‐hydroxyketone moiety using a (2R)‐hydroxymalonyl‐CoA extender unit. The modular PKS system contains a non‐canonical terminal module that lacks thioesterase (TE) and acyl carrier protein (ACP) domains, indicating the biosynthesis is likely to employ an unconventional and cryptic off‐loading mechanism that attaches glycine to the polyene‐polyol chain via an intermolecular amidation reaction.
The biosynthesis of octacosamicin A requires uncommon starter and extender units and likely employs an unusual mechanism for product release by catalysing an intermolecular amidation reaction.</description><subject>Acyl carrier protein</subject><subject>Biosynthesis</subject><subject>biosynthetic gene cluster</subject><subject>Fungicides</subject><subject>Glycine</subject><subject>guanidine</subject><subject>ketosynthase</subject><subject>Metabolites</subject><subject>Modular systems</subject><subject>Modular units</subject><subject>Molecular chains</subject><subject>Polyenes</subject><subject>Polyketide synthase</subject><subject>Polyketide Synthases - genetics</subject><subject>Polyketide Synthases - metabolism</subject><subject>Streptomycin</subject><issn>1439-4227</issn><issn>1439-7633</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi1ERUvhyhFZ4sIl6dje9drc0oiPSJVaFXq2HO8YXO3axfYW8u_ZKqFIXHqakeaZR6N5CXnDYMkA-JnbBrfkwAVAq-EZOWGN0ItOCvH80Decd8fkZSm3AKClYC_Iseg0KNZ1J6Sch1R2sf7AEgpNnl66al0qdgwuRLr6QG-iS-OYIv1aba6Yz_B3xdhjniehFmpjT69y6idX6TUOaEuI3-l9sHQTZ3xMA7ppsJmuxtDbGlJ8RY68HQq-PtRTcvPp47f1l8XF5efNenWxcEJxWDTQq45tHZcMWysbr7XvbdswLZxohVAeeg_IpJWy4a1Az7x0VmPTOhBai1Pyfu-9y-nnhKWaMRSHw2AjpqkYrlTLQTSqndF3_6G3acpxvs7w-VVaKi7VTC33lMuplIze3OUw2rwzDMxDHOYhDvMYx7zw9qCdtiP2j_jf_8-A3gO_woC7J3Rmfb5Z_5P_ARzklvU</recordid><startdate>20240102</startdate><enddate>20240102</enddate><creator>Liao, Yanghui</creator><creator>Wang, Xue‐Jiao</creator><creator>Ma, Guang‐Lei</creator><creator>Candra, Hartono</creator><creator>Qiu En, Sean Lee</creator><creator>Khandelwal, Srashti</creator><creator>Liang, Zhao‐Xun</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3128-1330</orcidid></search><sort><creationdate>20240102</creationdate><title>Biosynthesis of Octacosamicin A: Uncommon Starter/extender Units and Product Releasing via Intermolecular Amidation</title><author>Liao, Yanghui ; Wang, Xue‐Jiao ; Ma, Guang‐Lei ; Candra, Hartono ; Qiu En, Sean Lee ; Khandelwal, Srashti ; Liang, Zhao‐Xun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3820-40d871bc261e5a64f99fda54193c35338f0df0e16a664253ef1f6ca9e45c03993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acyl carrier protein</topic><topic>Biosynthesis</topic><topic>biosynthetic gene cluster</topic><topic>Fungicides</topic><topic>Glycine</topic><topic>guanidine</topic><topic>ketosynthase</topic><topic>Metabolites</topic><topic>Modular systems</topic><topic>Modular units</topic><topic>Molecular chains</topic><topic>Polyenes</topic><topic>Polyketide synthase</topic><topic>Polyketide Synthases - genetics</topic><topic>Polyketide Synthases - metabolism</topic><topic>Streptomycin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liao, Yanghui</creatorcontrib><creatorcontrib>Wang, Xue‐Jiao</creatorcontrib><creatorcontrib>Ma, Guang‐Lei</creatorcontrib><creatorcontrib>Candra, Hartono</creatorcontrib><creatorcontrib>Qiu En, Sean Lee</creatorcontrib><creatorcontrib>Khandelwal, Srashti</creatorcontrib><creatorcontrib>Liang, Zhao‐Xun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Chembiochem : a European journal of chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liao, Yanghui</au><au>Wang, Xue‐Jiao</au><au>Ma, Guang‐Lei</au><au>Candra, Hartono</au><au>Qiu En, Sean Lee</au><au>Khandelwal, Srashti</au><au>Liang, Zhao‐Xun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biosynthesis of Octacosamicin A: Uncommon Starter/extender Units and Product Releasing via Intermolecular Amidation</atitle><jtitle>Chembiochem : a European journal of chemical biology</jtitle><addtitle>Chembiochem</addtitle><date>2024-01-02</date><risdate>2024</risdate><volume>25</volume><issue>1</issue><spage>e202300590</spage><epage>n/a</epage><pages>e202300590-n/a</pages><issn>1439-4227</issn><eissn>1439-7633</eissn><abstract>Octacosamicin A is an antifungal metabolite featuring a linear polyene‐polyol chain flanked by N‐hydroxyguanidine and glycine moieties. We report here that sub‐inhibitory concentrations of streptomycin elicited the production of octacosamicin A in Amycolatopsis azurea DSM 43854T. We identified the biosynthetic gene cluster (oca BGC) that encodes a modular polyketide synthase (PKS) system for assembling the polyene‐polyol chain of octacosamicin A. Our analysis suggested that the N‐hydroxyguanidine unit originates from a 4‐guanidinobutyryl‐CoA starter unit, while the PKS incorporates an α‐hydroxyketone moiety using a (2R)‐hydroxymalonyl‐CoA extender unit. The modular PKS system contains a non‐canonical terminal module that lacks thioesterase (TE) and acyl carrier protein (ACP) domains, indicating the biosynthesis is likely to employ an unconventional and cryptic off‐loading mechanism that attaches glycine to the polyene‐polyol chain via an intermolecular amidation reaction.
The biosynthesis of octacosamicin A requires uncommon starter and extender units and likely employs an unusual mechanism for product release by catalysing an intermolecular amidation reaction.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37908177</pmid><doi>10.1002/cbic.202300590</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-3128-1330</orcidid></addata></record> |
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| subjects | Acyl carrier protein Biosynthesis biosynthetic gene cluster Fungicides Glycine guanidine ketosynthase Metabolites Modular systems Modular units Molecular chains Polyenes Polyketide synthase Polyketide Synthases - genetics Polyketide Synthases - metabolism Streptomycin |
| title | Biosynthesis of Octacosamicin A: Uncommon Starter/extender Units and Product Releasing via Intermolecular Amidation |
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