The Broad Aryl Acid Specificity of the Amide Bond Synthetase McbA Suggests Potential for the Biocatalytic Synthesis of Amides.

Autor: Petchey M; Department of Chemistry, University of York, York, YO10 5DD, UK., Cuetos A; Department of Chemistry, University of York, York, YO10 5DD, UK., Rowlinson B; Department of Chemistry, University of York, York, YO10 5DD, UK., Dannevald S; Department of Chemistry, University of York, York, YO10 5DD, UK., Frese A; Department of Chemistry, University of York, York, YO10 5DD, UK., Sutton PW; GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.; Current address: Department of Chemical, Biological and Environmental Engineering, Bioprocess Engineering and Applied Biocatalysis Group, Engineering School, Campus de la UAB, 08193 Bellaterra (Cerdanyola del Vallés), Barcelona, Spain., Lovelock S; GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.; Current address: School of Chemistry, University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, Manchester, M1 7DN, UK., Lloyd RC; GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK., Fairlamb IJS; Department of Chemistry, University of York, York, YO10 5DD, UK., Grogan G; Department of Chemistry, University of York, York, YO10 5DD, UK.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2018 Sep 03; Vol. 57 (36), pp. 11584-11588. Date of Electronic Publication: 2018 Aug 07.
DOI: 10.1002/anie.201804592
Abstrakt: 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.
(© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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