Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions

Three enzymatic routes toward γ-hydroxy-α-amino acids by tandem aldol addition–transamination one-pot two-step reactions are reported. The approaches feature an enantioselective aldol addition of pyruvate to various nonaromatic aldehydes catalyzed by trans-o-hydroxybenzylidene pyruvate hydratase-ald...

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Autores: Moreno, Carlos J., Hernández Sánchez, Karel, Charnock, Simon J., Gittings, Samantha, Bolte, Michael, Joglar Tamargo, Jesús, Bujons, Jordi, Parella, Teodor, Clapés Saborit, Pere
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2021
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/236791
Acesso em linha:http://hdl.handle.net/10261/236791
Access Level:Acceso aberto
Palavra-chave:Biocatalysis
2-oxoacid aldolases
Transaminases
Aldol adittion
Reductive amination
γ-hydroxy-α-amino acids
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spelling Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination ReactionsMoreno, Carlos J.Hernández Sánchez, KarelCharnock, Simon J.Gittings, SamanthaBolte, MichaelJoglar Tamargo, JesúsBujons, JordiParella, TeodorClapés Saborit, PereBiocatalysis2-oxoacid aldolasesTransaminasesAldol adittionReductive aminationγ-hydroxy-α-amino acidsThree enzymatic routes toward γ-hydroxy-α-amino acids by tandem aldol addition–transamination one-pot two-step reactions are reported. The approaches feature an enantioselective aldol addition of pyruvate to various nonaromatic aldehydes catalyzed by trans-o-hydroxybenzylidene pyruvate hydratase-aldolase (HBPA) from Pseudomonas putida. This affords chiral 4-hydroxy-2-oxo acids, which were subsequently enantioselectively aminated using S-selective transaminases. Three transamination processes were investigated involving different amine donors and transaminases: (i) l-Ala as an amine donor with pyruvate recycling, (ii) a benzylamine donor using benzaldehyde lyase from Pseudomonas fluorescens Biovar I (BAL) to transform the benzaldehyde formed into benzoin, minimizing equilibrium limitations, and (iii) l-Glu as an amine donor with a double cascade comprising branched-chain α-amino acid aminotransferase (BCAT) and aspartate amino transferase (AspAT), both from E. coli, using l-Asp as a substrate to regenerate l-Glu. The γ-hydroxy-α-amino acids thus obtained were transformed into chiral α-amino-γ-butyrolactones, structural motifs found in many biologically active compounds and valuable intermediates for the synthesis of pharmaceutical agents.This project has received funding from the Ministerio de Ciencia e Innovación (MICIN), cofinanced by the Fondo Europeo de Desarrollo Regional (FEDER) (grants RTI2018-094637-B-I00 to P.C. and PGC2018-095808-B-I00 to T.P.), and Programación Conjunta Internacional (PCI2018-092937), through the EU initiative ERA CoBioTech under grant agreement No [722361] to P.C and S.J.Ch.) (Tralaminol).Peer reviewedAmerican Chemical SocietyMinisterio de Ciencia e Innovación (España)European CommissionClapés Saborit, Pere [0000-0001-5541-4794]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/236791reponame: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#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-094637-B-I00 to P.C.info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-095808-B-I00 to T.P.info:eu-repo/grantAgreement/EC/H2020/722361https://doi.org/10.1021/acscatal.1c00210Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2367912026-05-22T06:33:51Z
dc.title.none.fl_str_mv Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
spellingShingle Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
Moreno, Carlos J.
Biocatalysis
2-oxoacid aldolases
Transaminases
Aldol adittion
Reductive amination
γ-hydroxy-α-amino acids
title_short Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title_full Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title_fullStr Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title_full_unstemmed Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title_sort Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
dc.creator.none.fl_str_mv Moreno, Carlos J.
Hernández Sánchez, Karel
Charnock, Simon J.
Gittings, Samantha
Bolte, Michael
Joglar Tamargo, Jesús
Bujons, Jordi
Parella, Teodor
Clapés Saborit, Pere
author Moreno, Carlos J.
author_facet Moreno, Carlos J.
Hernández Sánchez, Karel
Charnock, Simon J.
Gittings, Samantha
Bolte, Michael
Joglar Tamargo, Jesús
Bujons, Jordi
Parella, Teodor
Clapés Saborit, Pere
author_role author
author2 Hernández Sánchez, Karel
Charnock, Simon J.
Gittings, Samantha
Bolte, Michael
Joglar Tamargo, Jesús
Bujons, Jordi
Parella, Teodor
Clapés Saborit, Pere
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
European Commission
Clapés Saborit, Pere [0000-0001-5541-4794]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Biocatalysis
2-oxoacid aldolases
Transaminases
Aldol adittion
Reductive amination
γ-hydroxy-α-amino acids
topic Biocatalysis
2-oxoacid aldolases
Transaminases
Aldol adittion
Reductive amination
γ-hydroxy-α-amino acids
description Three enzymatic routes toward γ-hydroxy-α-amino acids by tandem aldol addition–transamination one-pot two-step reactions are reported. The approaches feature an enantioselective aldol addition of pyruvate to various nonaromatic aldehydes catalyzed by trans-o-hydroxybenzylidene pyruvate hydratase-aldolase (HBPA) from Pseudomonas putida. This affords chiral 4-hydroxy-2-oxo acids, which were subsequently enantioselectively aminated using S-selective transaminases. Three transamination processes were investigated involving different amine donors and transaminases: (i) l-Ala as an amine donor with pyruvate recycling, (ii) a benzylamine donor using benzaldehyde lyase from Pseudomonas fluorescens Biovar I (BAL) to transform the benzaldehyde formed into benzoin, minimizing equilibrium limitations, and (iii) l-Glu as an amine donor with a double cascade comprising branched-chain α-amino acid aminotransferase (BCAT) and aspartate amino transferase (AspAT), both from E. coli, using l-Asp as a substrate to regenerate l-Glu. The γ-hydroxy-α-amino acids thus obtained were transformed into chiral α-amino-γ-butyrolactones, structural motifs found in many biologically active compounds and valuable intermediates for the synthesis of pharmaceutical agents.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/236791
url http://hdl.handle.net/10261/236791
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#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-094637-B-I00 to P.C.
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-095808-B-I00 to T.P.
info:eu-repo/grantAgreement/EC/H2020/722361
https://doi.org/10.1021/acscatal.1c00210
Sí
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
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.198674

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