Spiroluchuene A Synthase: A Cyclase from Aspergillus luchuensis Forming a Spirotetracyclic Diterpene
The diterpene synthase AlTS was identified from Aspergillus luchuensis. AlTS catalyses the formation of the diterpene hydrocarbon spiroluchuene A, which exhibits a novel skeleton characterised by a spirocyclic ring system. The cyclisation mechanism towards this compound was elucidated through isotop...
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description | The diterpene synthase AlTS was identified from Aspergillus luchuensis. AlTS catalyses the formation of the diterpene hydrocarbon spiroluchuene A, which exhibits a novel skeleton characterised by a spirocyclic ring system. The cyclisation mechanism towards this compound was elucidated through isotopic labelling experiments in conjunction with DFT calculations and metadynamic simulations. The biosynthetic intermediate luchudiene, besides the derivative spiroluchuene B, was captured from an enzyme variant obtained through site‐directed mutagenesis. With its 10‐membered ring luchudiene is structurally related to germacrenes and can undergo a Cope rearrangement to luchuelemene.
A diterpene synthase for spiroluchuene A exhibiting a novel skeleton was discovered from Aspergillus luchuensis. Enzyme engineering through site‐directed mutagenesis allowed for the isolation of spiroluchuene B and the intermediate spiroluchuene. The enzyme mechanism was deeply studied through isotopic labelling experiments, DFT calculations and metadynamic simulations. The thermal reactions of luchudiene were studied. |
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A diterpene synthase for spiroluchuene A exhibiting a novel skeleton was discovered from Aspergillus luchuensis. Enzyme engineering through site‐directed mutagenesis allowed for the isolation of spiroluchuene B and the intermediate spiroluchuene. The enzyme mechanism was deeply studied through isotopic labelling experiments, DFT calculations and metadynamic simulations. The thermal reactions of luchudiene were studied.</description><edition>International ed. in English</edition><identifier>ISSN: 1433-7851</identifier><identifier>ISSN: 1521-3773</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.202315659</identifier><identifier>PMID: 37962519</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Aspergillus - genetics ; Aspergillus luchuensis ; Biosynthesis ; Cyclization ; Diterpenes ; Enzyme Mechanisms ; Hydrocarbons ; Isotope labelling ; Isotopes ; Labeling ; Mutagenesis ; Radioactive labelling ; Spirocycles ; Terpenoids</subject><ispartof>Angewandte Chemie International Edition, 2023-12, Vol.62 (52), p.e202315659-n/a</ispartof><rights>2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH</rights><rights>2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3739-7bb83322edc1755b5a295c862e4aa6daeec51ce39988bc55b8227e3c1016eb423</citedby><cites>FETCH-LOGICAL-c3739-7bb83322edc1755b5a295c862e4aa6daeec51ce39988bc55b8227e3c1016eb423</cites><orcidid>0000-0002-0102-0631</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%2Fanie.202315659$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fanie.202315659$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,1418,27928,27929,45578,45579</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37962519$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Zheng‐Yu</creatorcontrib><creatorcontrib>Taizoumbe, Kizerbo A.</creatorcontrib><creatorcontrib>Liang, Chengqin</creatorcontrib><creatorcontrib>Goldfuss, Bernd</creatorcontrib><creatorcontrib>Xu, Jian‐He</creatorcontrib><creatorcontrib>Dickschat, Jeroen S.</creatorcontrib><title>Spiroluchuene A Synthase: A Cyclase from Aspergillus luchuensis Forming a Spirotetracyclic Diterpene</title><title>Angewandte Chemie International Edition</title><addtitle>Angew Chem Int Ed Engl</addtitle><description>The diterpene synthase AlTS was identified from Aspergillus luchuensis. AlTS catalyses the formation of the diterpene hydrocarbon spiroluchuene A, which exhibits a novel skeleton characterised by a spirocyclic ring system. The cyclisation mechanism towards this compound was elucidated through isotopic labelling experiments in conjunction with DFT calculations and metadynamic simulations. The biosynthetic intermediate luchudiene, besides the derivative spiroluchuene B, was captured from an enzyme variant obtained through site‐directed mutagenesis. With its 10‐membered ring luchudiene is structurally related to germacrenes and can undergo a Cope rearrangement to luchuelemene.
A diterpene synthase for spiroluchuene A exhibiting a novel skeleton was discovered from Aspergillus luchuensis. Enzyme engineering through site‐directed mutagenesis allowed for the isolation of spiroluchuene B and the intermediate spiroluchuene. The enzyme mechanism was deeply studied through isotopic labelling experiments, DFT calculations and metadynamic simulations. The thermal reactions of luchudiene were studied.</description><subject>Aspergillus - genetics</subject><subject>Aspergillus luchuensis</subject><subject>Biosynthesis</subject><subject>Cyclization</subject><subject>Diterpenes</subject><subject>Enzyme Mechanisms</subject><subject>Hydrocarbons</subject><subject>Isotope labelling</subject><subject>Isotopes</subject><subject>Labeling</subject><subject>Mutagenesis</subject><subject>Radioactive labelling</subject><subject>Spirocycles</subject><subject>Terpenoids</subject><issn>1433-7851</issn><issn>1521-3773</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkDlPAzEQRi0E4gi0lMgSDc0GH_HapotCOCQERaC2vM4EjPbC3hXKv8chIUg0VPMVb55mPoROKRlSQtilrT0MGWGcilzoHXRIBaMZl5LvpjziPJNK0AN0FON74pUi-T464FLnTFB9iOaz1oem7N1bDzXgMZ4t6-7NRrhKebJ0ZYp4EZoKj2ML4dWXZR_xho8-4psmVL5-xRZ_mzrognVpzzt87TsIbdIeo72FLSOcbOYAvdxMnyd32cPT7f1k_JA5LrnOZFEozhmDuaNSiEJYpoVTOYORtfncAjhBHXCtlSpcAhRjErijhOZQjBgfoIu1tw3NRw-xM5WPDsrS1tD00aT3tdZcaJLQ8z_oe9OHOl1nmCZUK7kiB2i4plxoYgywMG3wlQ1LQ4lZ9W9W_Ztt_2nhbKPtiwrmW_yn8AToNfDpS1j-ozPjx_vpr_wLbO2SRQ</recordid><startdate>20231221</startdate><enddate>20231221</enddate><creator>Huang, Zheng‐Yu</creator><creator>Taizoumbe, Kizerbo A.</creator><creator>Liang, Chengqin</creator><creator>Goldfuss, Bernd</creator><creator>Xu, Jian‐He</creator><creator>Dickschat, Jeroen S.</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><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>7X8</scope><orcidid>https://orcid.org/0000-0002-0102-0631</orcidid></search><sort><creationdate>20231221</creationdate><title>Spiroluchuene A Synthase: A Cyclase from Aspergillus luchuensis Forming a Spirotetracyclic Diterpene</title><author>Huang, Zheng‐Yu ; Taizoumbe, Kizerbo A. ; Liang, Chengqin ; Goldfuss, Bernd ; Xu, Jian‐He ; Dickschat, Jeroen S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3739-7bb83322edc1755b5a295c862e4aa6daeec51ce39988bc55b8227e3c1016eb423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Aspergillus - genetics</topic><topic>Aspergillus luchuensis</topic><topic>Biosynthesis</topic><topic>Cyclization</topic><topic>Diterpenes</topic><topic>Enzyme Mechanisms</topic><topic>Hydrocarbons</topic><topic>Isotope labelling</topic><topic>Isotopes</topic><topic>Labeling</topic><topic>Mutagenesis</topic><topic>Radioactive labelling</topic><topic>Spirocycles</topic><topic>Terpenoids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Zheng‐Yu</creatorcontrib><creatorcontrib>Taizoumbe, Kizerbo A.</creatorcontrib><creatorcontrib>Liang, Chengqin</creatorcontrib><creatorcontrib>Goldfuss, Bernd</creatorcontrib><creatorcontrib>Xu, Jian‐He</creatorcontrib><creatorcontrib>Dickschat, Jeroen S.</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><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>MEDLINE - Academic</collection><jtitle>Angewandte Chemie International Edition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Zheng‐Yu</au><au>Taizoumbe, Kizerbo A.</au><au>Liang, Chengqin</au><au>Goldfuss, Bernd</au><au>Xu, Jian‐He</au><au>Dickschat, Jeroen S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spiroluchuene A Synthase: A Cyclase from Aspergillus luchuensis Forming a Spirotetracyclic Diterpene</atitle><jtitle>Angewandte Chemie International Edition</jtitle><addtitle>Angew Chem Int Ed Engl</addtitle><date>2023-12-21</date><risdate>2023</risdate><volume>62</volume><issue>52</issue><spage>e202315659</spage><epage>n/a</epage><pages>e202315659-n/a</pages><issn>1433-7851</issn><issn>1521-3773</issn><eissn>1521-3773</eissn><abstract>The diterpene synthase AlTS was identified from Aspergillus luchuensis. AlTS catalyses the formation of the diterpene hydrocarbon spiroluchuene A, which exhibits a novel skeleton characterised by a spirocyclic ring system. The cyclisation mechanism towards this compound was elucidated through isotopic labelling experiments in conjunction with DFT calculations and metadynamic simulations. The biosynthetic intermediate luchudiene, besides the derivative spiroluchuene B, was captured from an enzyme variant obtained through site‐directed mutagenesis. With its 10‐membered ring luchudiene is structurally related to germacrenes and can undergo a Cope rearrangement to luchuelemene.
A diterpene synthase for spiroluchuene A exhibiting a novel skeleton was discovered from Aspergillus luchuensis. Enzyme engineering through site‐directed mutagenesis allowed for the isolation of spiroluchuene B and the intermediate spiroluchuene. The enzyme mechanism was deeply studied through isotopic labelling experiments, DFT calculations and metadynamic simulations. The thermal reactions of luchudiene were studied.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37962519</pmid><doi>10.1002/anie.202315659</doi><tpages>9</tpages><edition>International ed. in English</edition><orcidid>https://orcid.org/0000-0002-0102-0631</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Aspergillus - genetics Aspergillus luchuensis Biosynthesis Cyclization Diterpenes Enzyme Mechanisms Hydrocarbons Isotope labelling Isotopes Labeling Mutagenesis Radioactive labelling Spirocycles Terpenoids |
title | Spiroluchuene A Synthase: A Cyclase from Aspergillus luchuensis Forming a Spirotetracyclic Diterpene |
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