Switching the substrate preference of fungal aryl-alcohol oxidase: towards stereoselective oxidation of secondary benzyl alcohols

Electronic supplementary information (ESI) available. See DOI: 10.1039/c8cy02447b

Detalles Bibliográficos
Autores: Serrano, Ana, Sancho, Ferran, Viña-González, Javier, Carro, Juan, Alcalde Galeote, Miguel, Guallar, Victor, Martínez, Ángel T.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/197214
Acceso en línea:http://hdl.handle.net/10261/197214
Access Level:acceso abierto
Palabra clave:Aryl-alcohol oxidase
Biological systems
Catalysis
Enzymology
Biotechnology
Catálisis
Enzimología
Biotecnología
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spelling Switching the substrate preference of fungal aryl-alcohol oxidase: towards stereoselective oxidation of secondary benzyl alcoholsSerrano, AnaSancho, FerranViña-González, JavierCarro, JuanAlcalde Galeote, MiguelGuallar, VictorMartínez, Ángel T.Aryl-alcohol oxidaseBiological systemsCatalysisEnzymologyBiotechnologyCatálisisEnzimologíaBiotecnologíaElectronic supplementary information (ESI) available. See DOI: 10.1039/c8cy02447b[EN] Oxidation of primary alcohols by aryl-alcohol oxidase (AAO), a flavoenzyme that provides H2O2 to fungal peroxidases for lignin degradation in nature, is achieved by concerted hydroxyl proton transfer and stereoselective hydride abstraction from the pro-R benzylic position. In racemic secondary alcohols, the R-hydrogen abstraction would result in the selective oxidation of the S-enantiomer to the corresponding ketone. This stereoselectivity of AAO may be exploited for enzymatic deracemization of chiral mixtures and isolation of R-enantiomers of industrial interest by switching the enzyme activity from primary to secondary alcohols. A combination of computational simulations and mutagenesis has been used to produce AAO variants with increased activity on secondary alcohols, using the already available F501A variant of Pleurotus eryngii AAO as a starting point. Adaptive-PELE simulations for the diffusion of (S)-1-(p-methoxyphenyl)-ethanol in this variant allowed Ile500 to be identified as one of the key residues with a higher number of contacts with the substrate during its transition from the solvent to the active site. Substitution of Ile500 produced more efficient variants for the oxidation of several secondary alcohols, and the I500M/F501W double variant was able to fully oxidize (after 75 min) with high selectivity (ee >99%) the S-enantiomer of the model secondary aryl-alcohol (±)-1-(p-methoxyphenyl)-ethanol, while the R-enantiomer remained unreacted.This work was supported by the INDOX (KBBE-2013-7-613549) EU project and by the BIO2017-86559-R (GenoBioref), CTQ2016-79138-R and BIO2016-79106-R projects of the Spanish Ministry of Economy, Industry and Competitiveness, cofinanced by FEDER funds. Pedro Merino (University of Zaragoza, Spain) is acknowledged for his suggestions on chiral HPLC analyses.Peer reviewedRoyal Society of Chemistry (UK)European CommissionMinisterio de Economía, Industria y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Alcalde Galeote, Miguel [0000-0001-6780-7616]Martínez, Ángel T.[0000-0002-1584-2863]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/197214reponame: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/FP7/613549info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BIO2017-86559-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2016-79138-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2016-79106-Rhttps://doi.org/10.1039/C8CY02447BSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1972142026-05-22T06:33:51Z
dc.title.none.fl_str_mv Switching the substrate preference of fungal aryl-alcohol oxidase: towards stereoselective oxidation of secondary benzyl alcohols
title Switching the substrate preference of fungal aryl-alcohol oxidase: towards stereoselective oxidation of secondary benzyl alcohols
spellingShingle Switching the substrate preference of fungal aryl-alcohol oxidase: towards stereoselective oxidation of secondary benzyl alcohols
Serrano, Ana
Aryl-alcohol oxidase
Biological systems
Catalysis
Enzymology
Biotechnology
Catálisis
Enzimología
Biotecnología
title_short Switching the substrate preference of fungal aryl-alcohol oxidase: towards stereoselective oxidation of secondary benzyl alcohols
title_full Switching the substrate preference of fungal aryl-alcohol oxidase: towards stereoselective oxidation of secondary benzyl alcohols
title_fullStr Switching the substrate preference of fungal aryl-alcohol oxidase: towards stereoselective oxidation of secondary benzyl alcohols
title_full_unstemmed Switching the substrate preference of fungal aryl-alcohol oxidase: towards stereoselective oxidation of secondary benzyl alcohols
title_sort Switching the substrate preference of fungal aryl-alcohol oxidase: towards stereoselective oxidation of secondary benzyl alcohols
dc.creator.none.fl_str_mv Serrano, Ana
Sancho, Ferran
Viña-González, Javier
Carro, Juan
Alcalde Galeote, Miguel
Guallar, Victor
Martínez, Ángel T.
author Serrano, Ana
author_facet Serrano, Ana
Sancho, Ferran
Viña-González, Javier
Carro, Juan
Alcalde Galeote, Miguel
Guallar, Victor
Martínez, Ángel T.
author_role author
author2 Sancho, Ferran
Viña-González, Javier
Carro, Juan
Alcalde Galeote, Miguel
Guallar, Victor
Martínez, Ángel T.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Ministerio de Economía, Industria y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Alcalde Galeote, Miguel [0000-0001-6780-7616]
Martínez, Ángel T.[0000-0002-1584-2863]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Aryl-alcohol oxidase
Biological systems
Catalysis
Enzymology
Biotechnology
Catálisis
Enzimología
Biotecnología
topic Aryl-alcohol oxidase
Biological systems
Catalysis
Enzymology
Biotechnology
Catálisis
Enzimología
Biotecnología
description Electronic supplementary information (ESI) available. See DOI: 10.1039/c8cy02447b
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
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/10261/197214
url http://hdl.handle.net/10261/197214
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/FP7/613549
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BIO2017-86559-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2016-79138-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2016-79106-R
https://doi.org/10.1039/C8CY02447B
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Royal Society of Chemistry (UK)
publisher.none.fl_str_mv Royal Society of Chemistry (UK)
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
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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