Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective Epoxidation

12 páginas.- 6 figuras.- 1 tabla.- 84 referencias.- The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscatal.0c03165

Detalles Bibliográficos
Autores: Municoy, Martí, González-Benjumea, Alejandro, Carro, Juan, Aranda, Carmen, Linde, Dolores, Renau-Mínguez, Chantal, Hofrichter, Martin, Guallar, Victor, Gutiérrez Suárez, Ana, Martínez, Ángel T.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::cbd1a8f9342a370ce761e4eb9d6d6de5
Acceso en línea:http://hdl.handle.net/10261/224429
Access Level:acceso abierto
Palabra clave:Adaptive-PELE
Computational chemistry
Fungal unspecific peroxygenases
Monte Carlo molecular simulations
Oxygenation patterns
Regioselective epoxidation
Stereoselective epoxidation
Unsaturated fatty acids
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dc.title.none.fl_str_mv Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective Epoxidation
title Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective Epoxidation
spellingShingle Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective Epoxidation
Municoy, Martí
Adaptive-PELE
Computational chemistry
Fungal unspecific peroxygenases
Monte Carlo molecular simulations
Oxygenation patterns
Regioselective epoxidation
Stereoselective epoxidation
Unsaturated fatty acids
title_short Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective Epoxidation
title_full Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective Epoxidation
title_fullStr Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective Epoxidation
title_full_unstemmed Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective Epoxidation
title_sort Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective Epoxidation
dc.creator.none.fl_str_mv Municoy, Martí
González-Benjumea, Alejandro
Carro, Juan
Aranda, Carmen
Linde, Dolores
Renau-Mínguez, Chantal
Hofrichter, Martin
Guallar, Victor
Gutiérrez Suárez, Ana
Martínez, Ángel T.
author Municoy, Martí
author_facet Municoy, Martí
González-Benjumea, Alejandro
Carro, Juan
Aranda, Carmen
Linde, Dolores
Renau-Mínguez, Chantal
Hofrichter, Martin
Guallar, Victor
Gutiérrez Suárez, Ana
Martínez, Ángel T.
author_role author
author2 González-Benjumea, Alejandro
Carro, Juan
Aranda, Carmen
Linde, Dolores
Renau-Mínguez, Chantal
Hofrichter, Martin
Guallar, Victor
Gutiérrez Suárez, Ana
Martínez, Ángel T.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Ministerio de Economía y Competitividad (España)
Generalitat de Catalunya
González-Benjumea, Alejandro [0000-0003-2857-9491]
Carro, Juan [0000-0002-7556-9782]
Aranda, Carmen [0000-0001-8213-1132]
Renau-Mínguez, Chantal [0000-0003-1308-7013]
Guallar, Victor [0000-0002-4580-1114]
Gutiérrez Suárez, Ana [0000-0002-8823-9029]
Martínez, Ángel T. [0000-0002-1584-2863]
Hofrichter, Martin [0000-0001-5174-7604]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Adaptive-PELE
Computational chemistry
Fungal unspecific peroxygenases
Monte Carlo molecular simulations
Oxygenation patterns
Regioselective epoxidation
Stereoselective epoxidation
Unsaturated fatty acids
topic Adaptive-PELE
Computational chemistry
Fungal unspecific peroxygenases
Monte Carlo molecular simulations
Oxygenation patterns
Regioselective epoxidation
Stereoselective epoxidation
Unsaturated fatty acids
description 12 páginas.- 6 figuras.- 1 tabla.- 84 referencias.- The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscatal.0c03165
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/224429
url http://hdl.handle.net/10261/224429
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2016-79138-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BIO2017-86559-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/ESF-2019-FI-B-00154
http://dx.doi.org/10.1021/acscatal.0c03165
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dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Fatty-Acid Oxygenation by Fungal Peroxygenases: From Computational Simulations to Preparative Regio- and Stereoselective EpoxidationMunicoy, MartíGonzález-Benjumea, AlejandroCarro, JuanAranda, CarmenLinde, DoloresRenau-Mínguez, ChantalHofrichter, MartinGuallar, VictorGutiérrez Suárez, AnaMartínez, Ángel T.Adaptive-PELEComputational chemistryFungal unspecific peroxygenasesMonte Carlo molecular simulationsOxygenation patternsRegioselective epoxidationStereoselective epoxidationUnsaturated fatty acids12 páginas.- 6 figuras.- 1 tabla.- 84 referencias.- The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscatal.0c03165Epoxidation of unsaturated fatty acids by unspecific peroxygenases (UPOs) of the best-known long-UPO subfamily, including the Agrocybe aegerita (AaeUPO) and Coprinopsis cinerea enzymes, is reported here. To understand the different oxygenation patterns by members of the long-UPO and short-UPO subfamilies, the latter represented by the Marasmius rotula enzyme (MroUPO), fatty-acid diffusion into their heme pockets was simulated with the adaptive PELE software. Computational results shed light on the inability of AaeUPO to epoxidize oleic acid (C18:1), opposed to MroUPO, due to steric hindrances to harbor (with a good interaction energy) the substrate with the Δ9 C10 atom at a catalytically relevant distance (<3.5 Å) from the oxo group in simulated heme compound-I. However, effective α-linolenic acid epoxidation is anticipated because the Δ15 C16 atom would attain such a distance in AaeUPO thanks to its more terminal position. The above hypothesis was verified using an engineered MroUPO variant (I153F/S156F) with a narrowed heme access channel mimicking that of AaeUPO. Experimental oxygenation of unsaturated fatty acids by this variant thus resembles that of AaeUPO, including regioselective (from 95% to >99%) formation of cis,cis-15,16-epoxyoctadeca-9,12-dienoic acid. The nearly complete conversion of α-linolenic acid by the two enzymes was transferred to a small preparative scale, the yield of purified product was estimated, its chemical structure analyzed by NMR, and more interestingly, stereoselective production of the 15(R),16(S) enantiomer (80-83% ee) assessed by chiral HPLC. This enzymatic synthesis overcomes the unspecificity of chemical epoxidation where the reaction cannot be restricted to the formation of monoepoxides as found during m-perchlorobenzoic acid oxidation of α-linolenic acid. Moreover, the variant was able to produce the unsaturated dicarboxylic fatty acid, together with subterminal oxygenation products, during partial conversion of oleic acid. These two noteworthy reactions had not been reported for any UPO described to date. © 2020 American Chemical Society. All rights reserved.This work has received funding from the Bio Based Industries Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 792063 (“Development and pilot production of sustainable binder systems for wood based panels”, https://susbind.eu ), the CTQ2016-79138-R and BIO2017-86559-R projects of Spanish MINECO, the Secretaria d’Universitats i Recerca of Generalitat de Catalunya, and the European Social Fund (ESF-2019-FI-B-00154). The authors thank Novozymes A/S for supplying r CciUPO. MM acknowledges a Catalan Government doctoral grant.Peer reviewedAmerican Chemical SocietyEuropean CommissionMinisterio de Economía y Competitividad (España)Generalitat de CatalunyaGonzález-Benjumea, Alejandro [0000-0003-2857-9491]Carro, Juan [0000-0002-7556-9782]Aranda, Carmen [0000-0001-8213-1132]Renau-Mínguez, Chantal [0000-0003-1308-7013]Guallar, Victor [0000-0002-4580-1114]Gutiérrez Suárez, Ana [0000-0002-8823-9029]Martínez, Ángel T. [0000-0002-1584-2863]Hofrichter, Martin [0000-0001-5174-7604]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/224429reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/H2020/792063info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2016-79138-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BIO2017-86559-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/ESF-2019-FI-B-00154http://dx.doi.org/10.1021/acscatal.0c03165Síinfo:eu-repo/semantics/openAccessoai:dnet:digitalcsic_::cbd1a8f9342a370ce761e4eb9d6d6de52026-05-22T06:33:51Z
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