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dc.contributor.authorLinde, Dolores
dc.contributor.authorCañellas, Marina
dc.contributor.authorCoscolín, Cristina
dc.contributor.authorDavó-Siguero, Irene
dc.contributor.authorRomero, Antonio
dc.contributor.authorLucas, Fátima
dc.contributor.authorRuiz-Dueñas, Francisco J.
dc.contributor.authorGuallar, Víctor
dc.contributor.authorMartínez, Ángel T.
dc.contributor.otherBarcelona Supercomputing Center
dc.date.accessioned2016-06-07T09:35:07Z
dc.date.available2016-06-07T09:35:07Z
dc.date.issued2016-05-23
dc.identifier.citationLinde, Dolores [et al.]. Asymmetric sulfoxidation by engineering the heme pocket of a dye-decolorizing peroxidase. "Catalysis Science & Technology", 23 Maig 2016.
dc.identifier.issn2044-4753
dc.identifier.urihttp://hdl.handle.net/2117/87761
dc.description.abstractThe so-called dye-decolorizing peroxidases (DyPs) constitute a new family of proteins exhibiting remarkable stability. With the aim of providing them new catalytic activities of biotechnological interest, the heme pocket of one of the few DyPs fully characterized to date (from the fungus Auricularia auricula-judae) was redesigned based on the crystal structure available, and its potential for asymmetric sulfoxidation was evaluated. Chiral sulfoxides are important targets in organic synthesis and enzyme catalysis, due to a variety of applications. Interestingly, one of the DyP variants, F359G, is highly stereoselective in sulfoxidizing methylphenyl sulfide and methyl-p-tolyl sulfide (95–99% conversion, with up to 99% excess of the S enantiomer in short reaction times), while the parent DyP has no sulfoxidation activity, and the L357G variant produces both R and S enantiomers. The two variants were crystallized, and their crystal structures were used in molecular simulations to provide a rational explanation for the new catalytic activities. Protein energy landscape exploration (PELE) showed more favorable protein–substrate catalytic complexes for the above variants, with a considerable number of structures near the oxygen atom of the activated heme, which is incorporated into the substrates as shown in 18O-labeling experiments, and improved affinity with respect to the parent enzyme, explaining their sulfoxidation activity. Additional quantum mechanics/molecular mechanics (QM/MM) calculations were performed to elucidate the high stereoselectivity observed for the F359G variant, which correlated with higher reactivity on the substrate molecules adopting pro-S poses at the active site. Similar computational analyses can help introduce/improve (stereoselective) sulfoxidation activity in related hemeproteins.
dc.description.sponsorshipThis work was supported by the INDOX (KBBE-2013-7-613549) EU project and by the BIO2014-56388-R (NOESIS), BFU2014-55448-P and CTQ2013-48287-R projects of the Spanish Ministry of Economy and Competitiveness (MINECO). Pedro Merino (University of Zaragoza, Spain) is acknowledged for his suggestions on chiral HPLC analyses, and Alicia Prieto and Leonor Rodríguez (CIB, Madrid, Spain) for their help in GC-MS analyses. We cordially thank the staff at ID23-1 beamline (ESRF) and the BL13-XALOC beamline (ALBA). F. J. R.-D. acknowledges a MINECO Ramón & Cajal contract.
dc.format.extent9 p.
dc.language.isoeng
dc.publisherRoyal Society of Chemistry
dc.rightsAttribution-NonCommercial-NoDerivs 4.0 Spain
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/es/
dc.subjectÀrees temàtiques de la UPC::Enginyeria electrònica
dc.subject.lcshOxidation
dc.subject.lcshPeroxidase--Analysis
dc.subject.lcshProteins
dc.subject.otherDye-decolorizing peroxidases (DyPs)
dc.subject.otherProteins
dc.subject.otherCatalytic activities
dc.subject.otherOxidation reaction
dc.titleAsymmetric sulfoxidation by engineering the heme pocket of a dye-decolorizing peroxidase
dc.typeArticle
dc.subject.lemacOxidació
dc.subject.lemacProteïnes
dc.identifier.doi10.1039/c6cy00539j
dc.description.peerreviewedPeer Reviewed
dc.relation.publisherversionhttp://pubs.rsc.org/en/content/articlelanding/2016/cy/c6cy00539j#!divAbstract
dc.rights.accessOpen Access
dc.description.versionPostprint (published version)
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7/613549/EU/Optimized oxidoreductases for medium and large scale industrial biotransformations/INDOX
dc.relation.projectidinfo:eu-repo/grantAgreement/MINECO//BIO2014-56388-R/ES/NUEVAS ENZIMAS OXIDATIVAS PARA UNA INDUSTRIA SOSTENIBLE/
dc.relation.projectidinfo:eu-repo/grantAgreement/MINECO//BFU2014-55448-P/ES/DESENMASCARANDO PATOGENICIDAD Y VIRULENCIA EN ACINETOBACTER BAUMANNII: UNA APROXIMACION ESTRUCTURAL/
dc.relation.projectidinfo:eu-repo/grantAgreement/MINECO//CTQ2013-48287-R/ES/DISENYO COMPUTACIONAL RACIONAL DE OXIDOREDUCTASAS PARA APLICACIONES INDUSTRIALES Y TECNOLOGICAS/
local.citation.publicationNameCatalysis Science & Technology


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