Harnessing and engineering amide bond forming ligases for the synthesis of amides.


Journal

Current opinion in chemical biology
ISSN: 1879-0402
Titre abrégé: Curr Opin Chem Biol
Pays: England
ID NLM: 9811312

Informations de publication

Date de publication:
04 2020
Historique:
received: 14 10 2019
revised: 06 12 2019
accepted: 12 12 2019
pubmed: 15 2 2020
medline: 13 2 2021
entrez: 15 2 2020
Statut: ppublish

Résumé

The amide functional group is ubiquitous in nature and one of the most important motifs in pharmaceuticals, agrochemicals, and other valuable products. While coupling amides and carboxylic acids is a trivial synthetic transformation, it often requires protective group manipulation, along with stoichiometric quantities of expensive and deleterious coupling reagents. Nature has evolved a range of enzymes to construct amide bonds, the vast majority of which utilize adenosine triphosphate to activate the carboxylic acid substrate for amine coupling. Despite the fact that these enzymes operate under mild conditions, as well as possessing chemoselectivity and regioselectivity that obviates the need for protecting groups, their synthetic potential has been largely unexplored. In this review, we discuss recent research into the discovery, characterization, and development of amide bond forming enzymes, with an emphasis on stand-alone ligase enzymes that can generate amides directly from simple carboxylic acid and amine substrates.

Identifiants

pubmed: 32058241
pii: S1367-5931(19)30148-6
doi: 10.1016/j.cbpa.2019.12.004
pii:
doi:

Substances chimiques

Amides 0
Amines 0
Carboxylic Acids 0
Adenosine Triphosphate 8L70Q75FXE
Acyltransferases EC 2.3.-
Amide Synthases EC 6.3.1.-
Peptide Synthases EC 6.3.2.-
non-ribosomal peptide synthase EC 6.3.2.-
Coenzyme A SAA04E81UX

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

77-85

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/K002341/1
Pays : United Kingdom

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement Nothing declared.

Auteurs

Michael Winn (M)

School of Chemistry and Manchester Institute of Biotechnology (MIB), The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.

Shona M Richardson (SM)

School of Chemistry, University of Edinburgh, David Brewster Road, King's Buildings, Edinburgh, EH9 3FJ, UK.

Dominic J Campopiano (DJ)

School of Chemistry, University of Edinburgh, David Brewster Road, King's Buildings, Edinburgh, EH9 3FJ, UK. Electronic address: Dominic.Campopiano@ed.ac.uk.

Jason Micklefield (J)

School of Chemistry and Manchester Institute of Biotechnology (MIB), The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK. Electronic address: jason.micklefield@manchester.ac.uk.

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Classifications MeSH