Grogan, Gideon James orcid.org/0000-0003-1383-7056, Petchey, Mark, Cuetos, Anibal et al. (7 more authors) (2018) The Broad Aryl Acid Specificity of the Amide Bond Synthetase McbA Suggests Potential for the Biocatalytic Synthesis of Amides. Angewandte Chemie International Edition. pp. 11584-11588. ISSN 1433-7851
Abstract
Amide bond formation is one of the most important reactions in pharmaceutical synthetic chemistry. The development of sustainable methods of amide bond formation, including those that are catalyzed by enzymes, is therefore of significant interest. The ATP-dependent amide bond synthetase (ABS) enzyme McbA, from Marinactinospora thermotolerans, catalyzes the formation of amides as part of the biosynthetic pathway towards the marinacarboline secondary metabolites. The reaction proceeds via an adenylate intermediate, with both adenylation and amidation steps catalyzed within one active site. In this study, McbA has been applied to the synthesis of pharmaceutical-type amides from a range of aryl carboxylic acids with partner amines provided at 1-5 molar equivalents. The structure of McbA has revealed the structural determinants of aryl acid substrate tolerance and differences in conformation associated with the two half-reactions catalyzed. The catalytic performance of McbA, coupled with the structure, suggest that this and other ABS enzymes may be engineered for applications in the sustainable synthesis of pharmaceutically relevant (chiral) amides.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Wiley-VCH Verlag GmbH &Co. KGaA,Weinheim. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. |
Keywords: | ATP,adenylation,amides,biocatalysis,ligases |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 24 Aug 2018 08:20 |
Last Modified: | 16 Oct 2024 14:56 |
Published Version: | https://doi.org/10.1002/anie.201804592 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1002/anie.201804592 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:134973 |