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The Broad Aryl Acid Specificity of the Amide Bond Synthetase McbA Suggests Potential for the Biocatalytic Synthesis of Amides
Petchey, Mark (University of York)
Cuetos, Anibal (University of York)
Rowlinson, Benjamin (University of York)
Dannevald, Stephanie (University of York)
Frese, Amina (University of York)
Sutton, Peter W. (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Lovelock, Sarah (University of Manchester)
Lloyd, Richard C. (GSK Medicines Research Centre)
Fairlamb, Ian J. S. (University of York)
Grogan, Gideon (University of York)

Date: 2018
Abstract: Amide bond formation is one of the most important reactions in pharmaceutical synthetic chemistry. The development of sustainable methods for 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 was 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 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.
Language: Anglès
Document: article ; recerca ; publishedVersion
Subject: Adenylation ; Amides ; ATP ; Biocatalysis ; Ligases
Published in: Angewandte Chemie (International ed. Internet), Vol. 57 (august 2018) , p. 11584-11588, ISSN 1521-3773

DOI: 10.1002/anie.201804592
PMID: 30035356


5 p, 1.9 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles

 Record created 2020-07-13, last modified 2020-12-23



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