Reversible Product Release and Recapture by a Fungal Polyketide Synthase Using a Carnitine Acyltransferase Domain
Fungal polyketides have significant biological activities, yet the biosynthesis by highly reducing polyketide synthases (HRPKSs) remains enigmatic. An uncharacterized group of HRPKSs was found to contain a C‐terminal domain with significant homology to carnitine O‐acyltransferase (cAT). Characteriza...
Gespeichert in:
| Veröffentlicht in: | Angewandte Chemie International Edition 2017-08, Vol.56 (32), p.9556-9560 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 9560 |
|---|---|
| container_issue | 32 |
| container_start_page | 9556 |
| container_title | Angewandte Chemie International Edition |
| container_volume | 56 |
| creator | Hang, Leibniz Tang, Man‐Cheng Harvey, Colin J. B. Page, Claire G. Li, Jian Hung, Yiu‐Sun Liu, Nicholas Hillenmeyer, Maureen E. Tang, Yi |
| description | Fungal polyketides have significant biological activities, yet the biosynthesis by highly reducing polyketide synthases (HRPKSs) remains enigmatic. An uncharacterized group of HRPKSs was found to contain a C‐terminal domain with significant homology to carnitine O‐acyltransferase (cAT). Characterization of one such HRPKS (Tv6‐931) from Trichoderma virens showed that the cAT domain is capable of esterifying the polyketide product with polyalcohol nucleophiles. This process is readily reversible, as confirmed through the holo ACP‐dependent transesterification of the released product. The methyltransferase (MT) domain of Tv6‐931 can perform two consecutive α‐methylation steps on the last β‐keto intermediate to yield an α,α‐gem‐dimethyl product, a new programing feature among HRPKSs. Recapturing of the released product by cAT domain is suggested to facilitate complete gem‐dimethylation by the MT.
An uncharacterized group of highly reducing polyketide synthases (HRPKSs) contains a C‐terminal domain with significant homology to carnitine O‐acyltransferase (cAT). Characterization of one such HRPKS (Tv6‐931) from Trichoderma virens showed that the cAT domain is capable of esterifying the polyketide product with polyalcohol nucleophiles. |
| doi_str_mv | 10.1002/anie.201705237 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5580239</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1923616147</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4727-cf6ea661f2237ff1001cfd90dba4b774d761b7a3af450fcd568abe5f8faeb61f3</originalsourceid><addsrcrecordid>eNqFkctv1DAQxi0Eog-4ckSWOGfxI7GTC9Jq-6BSBVWhZ2vijLcuWWdrJ0X57_FqywInTjPS_Oabb_QR8o6zBWdMfITgcSEY16wSUr8gx7wSvJBay5e5L6UsdF3xI3KS0kPm65qp1-RI1Eo3TLJj8niLTxiTb3ukN3HoJjvSW-wRElIIXe4tbMcpIm1nCvRiCmvo6c3Qzz9w9B3Sb3MY73f0XfJhnZEVxOBHH5Au7dyPEUJyGHfE2bABH96QVw76hG-f6ym5uzj_vvpcXH-9vFotrwtbaqEL6xSCUtyJ_Jdz-VluXdewroWy1brstOKtBgmurJizXaVqaLFytQNs85o8JZ_2utup3WBnMWQvvdlGv4E4mwG8-XcS_L1ZD0-mqmomZJMFPjwLxOFxwjSah2GKIXs2vBFSccVLnanFnrJxSCmiO1zgzOwiMruIzCGivPD-b18H_HcmGWj2wE_f4_wfObP8cnX-R_wXRmag_A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1923616147</pqid></control><display><type>article</type><title>Reversible Product Release and Recapture by a Fungal Polyketide Synthase Using a Carnitine Acyltransferase Domain</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Hang, Leibniz ; Tang, Man‐Cheng ; Harvey, Colin J. B. ; Page, Claire G. ; Li, Jian ; Hung, Yiu‐Sun ; Liu, Nicholas ; Hillenmeyer, Maureen E. ; Tang, Yi</creator><creatorcontrib>Hang, Leibniz ; Tang, Man‐Cheng ; Harvey, Colin J. B. ; Page, Claire G. ; Li, Jian ; Hung, Yiu‐Sun ; Liu, Nicholas ; Hillenmeyer, Maureen E. ; Tang, Yi</creatorcontrib><description>Fungal polyketides have significant biological activities, yet the biosynthesis by highly reducing polyketide synthases (HRPKSs) remains enigmatic. An uncharacterized group of HRPKSs was found to contain a C‐terminal domain with significant homology to carnitine O‐acyltransferase (cAT). Characterization of one such HRPKS (Tv6‐931) from Trichoderma virens showed that the cAT domain is capable of esterifying the polyketide product with polyalcohol nucleophiles. This process is readily reversible, as confirmed through the holo ACP‐dependent transesterification of the released product. The methyltransferase (MT) domain of Tv6‐931 can perform two consecutive α‐methylation steps on the last β‐keto intermediate to yield an α,α‐gem‐dimethyl product, a new programing feature among HRPKSs. Recapturing of the released product by cAT domain is suggested to facilitate complete gem‐dimethylation by the MT.
An uncharacterized group of highly reducing polyketide synthases (HRPKSs) contains a C‐terminal domain with significant homology to carnitine O‐acyltransferase (cAT). Characterization of one such HRPKS (Tv6‐931) from Trichoderma virens showed that the cAT domain is capable of esterifying the polyketide product with polyalcohol nucleophiles.</description><edition>International ed. in English</edition><identifier>ISSN: 1433-7851</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.201705237</identifier><identifier>PMID: 28679030</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Acyltransferase ; Biocatalysis ; Biological Products - chemistry ; Biological Products - metabolism ; Biosynthesis ; Carnitine ; Carnitine Acyltransferases - metabolism ; Catalytic Domain ; Esterification ; Fungi ; heterologous expression ; Homology ; Metabolomics ; Methylation ; Methyltransferase ; Molecular Structure ; Nucleophiles ; Polyketide synthase ; Polyketide Synthases - metabolism ; Polyketides ; Transesterification ; Trichoderma - enzymology</subject><ispartof>Angewandte Chemie International Edition, 2017-08, Vol.56 (32), p.9556-9560</ispartof><rights>2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4727-cf6ea661f2237ff1001cfd90dba4b774d761b7a3af450fcd568abe5f8faeb61f3</citedby><cites>FETCH-LOGICAL-c4727-cf6ea661f2237ff1001cfd90dba4b774d761b7a3af450fcd568abe5f8faeb61f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fanie.201705237$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fanie.201705237$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28679030$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hang, Leibniz</creatorcontrib><creatorcontrib>Tang, Man‐Cheng</creatorcontrib><creatorcontrib>Harvey, Colin J. B.</creatorcontrib><creatorcontrib>Page, Claire G.</creatorcontrib><creatorcontrib>Li, Jian</creatorcontrib><creatorcontrib>Hung, Yiu‐Sun</creatorcontrib><creatorcontrib>Liu, Nicholas</creatorcontrib><creatorcontrib>Hillenmeyer, Maureen E.</creatorcontrib><creatorcontrib>Tang, Yi</creatorcontrib><title>Reversible Product Release and Recapture by a Fungal Polyketide Synthase Using a Carnitine Acyltransferase Domain</title><title>Angewandte Chemie International Edition</title><addtitle>Angew Chem Int Ed Engl</addtitle><description>Fungal polyketides have significant biological activities, yet the biosynthesis by highly reducing polyketide synthases (HRPKSs) remains enigmatic. An uncharacterized group of HRPKSs was found to contain a C‐terminal domain with significant homology to carnitine O‐acyltransferase (cAT). Characterization of one such HRPKS (Tv6‐931) from Trichoderma virens showed that the cAT domain is capable of esterifying the polyketide product with polyalcohol nucleophiles. This process is readily reversible, as confirmed through the holo ACP‐dependent transesterification of the released product. The methyltransferase (MT) domain of Tv6‐931 can perform two consecutive α‐methylation steps on the last β‐keto intermediate to yield an α,α‐gem‐dimethyl product, a new programing feature among HRPKSs. Recapturing of the released product by cAT domain is suggested to facilitate complete gem‐dimethylation by the MT.
An uncharacterized group of highly reducing polyketide synthases (HRPKSs) contains a C‐terminal domain with significant homology to carnitine O‐acyltransferase (cAT). Characterization of one such HRPKS (Tv6‐931) from Trichoderma virens showed that the cAT domain is capable of esterifying the polyketide product with polyalcohol nucleophiles.</description><subject>Acyltransferase</subject><subject>Biocatalysis</subject><subject>Biological Products - chemistry</subject><subject>Biological Products - metabolism</subject><subject>Biosynthesis</subject><subject>Carnitine</subject><subject>Carnitine Acyltransferases - metabolism</subject><subject>Catalytic Domain</subject><subject>Esterification</subject><subject>Fungi</subject><subject>heterologous expression</subject><subject>Homology</subject><subject>Metabolomics</subject><subject>Methylation</subject><subject>Methyltransferase</subject><subject>Molecular Structure</subject><subject>Nucleophiles</subject><subject>Polyketide synthase</subject><subject>Polyketide Synthases - metabolism</subject><subject>Polyketides</subject><subject>Transesterification</subject><subject>Trichoderma - enzymology</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctv1DAQxi0Eog-4ckSWOGfxI7GTC9Jq-6BSBVWhZ2vijLcuWWdrJ0X57_FqywInTjPS_Oabb_QR8o6zBWdMfITgcSEY16wSUr8gx7wSvJBay5e5L6UsdF3xI3KS0kPm65qp1-RI1Eo3TLJj8niLTxiTb3ukN3HoJjvSW-wRElIIXe4tbMcpIm1nCvRiCmvo6c3Qzz9w9B3Sb3MY73f0XfJhnZEVxOBHH5Au7dyPEUJyGHfE2bABH96QVw76hG-f6ym5uzj_vvpcXH-9vFotrwtbaqEL6xSCUtyJ_Jdz-VluXdewroWy1brstOKtBgmurJizXaVqaLFytQNs85o8JZ_2utup3WBnMWQvvdlGv4E4mwG8-XcS_L1ZD0-mqmomZJMFPjwLxOFxwjSah2GKIXs2vBFSccVLnanFnrJxSCmiO1zgzOwiMruIzCGivPD-b18H_HcmGWj2wE_f4_wfObP8cnX-R_wXRmag_A</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Hang, Leibniz</creator><creator>Tang, Man‐Cheng</creator><creator>Harvey, Colin J. B.</creator><creator>Page, Claire G.</creator><creator>Li, Jian</creator><creator>Hung, Yiu‐Sun</creator><creator>Liu, Nicholas</creator><creator>Hillenmeyer, Maureen E.</creator><creator>Tang, Yi</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>7TM</scope><scope>K9.</scope><scope>5PM</scope></search><sort><creationdate>20170801</creationdate><title>Reversible Product Release and Recapture by a Fungal Polyketide Synthase Using a Carnitine Acyltransferase Domain</title><author>Hang, Leibniz ; Tang, Man‐Cheng ; Harvey, Colin J. B. ; Page, Claire G. ; Li, Jian ; Hung, Yiu‐Sun ; Liu, Nicholas ; Hillenmeyer, Maureen E. ; Tang, Yi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4727-cf6ea661f2237ff1001cfd90dba4b774d761b7a3af450fcd568abe5f8faeb61f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acyltransferase</topic><topic>Biocatalysis</topic><topic>Biological Products - chemistry</topic><topic>Biological Products - metabolism</topic><topic>Biosynthesis</topic><topic>Carnitine</topic><topic>Carnitine Acyltransferases - metabolism</topic><topic>Catalytic Domain</topic><topic>Esterification</topic><topic>Fungi</topic><topic>heterologous expression</topic><topic>Homology</topic><topic>Metabolomics</topic><topic>Methylation</topic><topic>Methyltransferase</topic><topic>Molecular Structure</topic><topic>Nucleophiles</topic><topic>Polyketide synthase</topic><topic>Polyketide Synthases - metabolism</topic><topic>Polyketides</topic><topic>Transesterification</topic><topic>Trichoderma - enzymology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hang, Leibniz</creatorcontrib><creatorcontrib>Tang, Man‐Cheng</creatorcontrib><creatorcontrib>Harvey, Colin J. B.</creatorcontrib><creatorcontrib>Page, Claire G.</creatorcontrib><creatorcontrib>Li, Jian</creatorcontrib><creatorcontrib>Hung, Yiu‐Sun</creatorcontrib><creatorcontrib>Liu, Nicholas</creatorcontrib><creatorcontrib>Hillenmeyer, Maureen E.</creatorcontrib><creatorcontrib>Tang, Yi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Angewandte Chemie International Edition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hang, Leibniz</au><au>Tang, Man‐Cheng</au><au>Harvey, Colin J. B.</au><au>Page, Claire G.</au><au>Li, Jian</au><au>Hung, Yiu‐Sun</au><au>Liu, Nicholas</au><au>Hillenmeyer, Maureen E.</au><au>Tang, Yi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reversible Product Release and Recapture by a Fungal Polyketide Synthase Using a Carnitine Acyltransferase Domain</atitle><jtitle>Angewandte Chemie International Edition</jtitle><addtitle>Angew Chem Int Ed Engl</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>56</volume><issue>32</issue><spage>9556</spage><epage>9560</epage><pages>9556-9560</pages><issn>1433-7851</issn><eissn>1521-3773</eissn><abstract>Fungal polyketides have significant biological activities, yet the biosynthesis by highly reducing polyketide synthases (HRPKSs) remains enigmatic. An uncharacterized group of HRPKSs was found to contain a C‐terminal domain with significant homology to carnitine O‐acyltransferase (cAT). Characterization of one such HRPKS (Tv6‐931) from Trichoderma virens showed that the cAT domain is capable of esterifying the polyketide product with polyalcohol nucleophiles. This process is readily reversible, as confirmed through the holo ACP‐dependent transesterification of the released product. The methyltransferase (MT) domain of Tv6‐931 can perform two consecutive α‐methylation steps on the last β‐keto intermediate to yield an α,α‐gem‐dimethyl product, a new programing feature among HRPKSs. Recapturing of the released product by cAT domain is suggested to facilitate complete gem‐dimethylation by the MT.
An uncharacterized group of highly reducing polyketide synthases (HRPKSs) contains a C‐terminal domain with significant homology to carnitine O‐acyltransferase (cAT). Characterization of one such HRPKS (Tv6‐931) from Trichoderma virens showed that the cAT domain is capable of esterifying the polyketide product with polyalcohol nucleophiles.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28679030</pmid><doi>10.1002/anie.201705237</doi><tpages>5</tpages><edition>International ed. in English</edition><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1433-7851 |
| ispartof | Angewandte Chemie International Edition, 2017-08, Vol.56 (32), p.9556-9560 |
| issn | 1433-7851 1521-3773 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5580239 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Acyltransferase Biocatalysis Biological Products - chemistry Biological Products - metabolism Biosynthesis Carnitine Carnitine Acyltransferases - metabolism Catalytic Domain Esterification Fungi heterologous expression Homology Metabolomics Methylation Methyltransferase Molecular Structure Nucleophiles Polyketide synthase Polyketide Synthases - metabolism Polyketides Transesterification Trichoderma - enzymology |
| title | Reversible Product Release and Recapture by a Fungal Polyketide Synthase Using a Carnitine Acyltransferase Domain |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T04%3A39%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Reversible%20Product%20Release%20and%20Recapture%20by%20a%20Fungal%20Polyketide%20Synthase%20Using%20a%20Carnitine%20Acyltransferase%20Domain&rft.jtitle=Angewandte%20Chemie%20International%20Edition&rft.au=Hang,%20Leibniz&rft.date=2017-08-01&rft.volume=56&rft.issue=32&rft.spage=9556&rft.epage=9560&rft.pages=9556-9560&rft.issn=1433-7851&rft.eissn=1521-3773&rft_id=info:doi/10.1002/anie.201705237&rft_dat=%3Cproquest_pubme%3E1923616147%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1923616147&rft_id=info:pmid/28679030&rfr_iscdi=true |