Sharma, Mahima orcid.org/0000-0003-3960-2212, Mangas-Sanchez, Juan, France, Scott et al. (5 more authors) (2018) A Mechanism for Reductive Amination Catalyzed by Fungal Reductive Aminases (RedAms). ACS Catalysis. 11534–11541. ISSN 2155-5435
Abstract
Reductive Aminases (RedAms) catalyze the asymmetric reductive amination of ketones with primary amines to give secondary amine products. RedAms have great potential for the synthesis of bioactive chiral amines, however, insights into their mechanism are currently limited. Comparative studies on reductive amination of cyclohexanone with allylamine in the presence of RedAms, imine reductases (IREDs) or NaBH3CN support the distinctive activity of RedAms in catalyzing both imine formation and reduction in the reaction. Structures of AtRedAm from Aspergillus terreus, in complex with NADPH and ketone and amine substrates, along with kinetic analysis of active-site mutants, reveal modes of substrate binding, the basis for the specificity of RedAms for reduction of imines over ketones, and the importance of domain flexibility in bringing the reactive participants together for the reaction. This information is used to propose a mechanism for their action and also to expand the substrate specificity of RedAms using protein engineering.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 American Chemical Society. 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. |
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: | 08 Nov 2018 09:20 |
Last Modified: | 08 Feb 2025 00:32 |
Published Version: | https://doi.org/10.1021/acscatal.8b03491 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1021/acscatal.8b03491 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:138371 |