Grogan, Gideon James orcid.org/0000-0003-1383-7056, Frese, Amina, Turkenburg, Johan et al. (11 more authors) (2019) A family of Native Amine Dehydrogenases for the Asymmetric Reductive Amination of Ketones. Nature Catalysis. pp. 324-333. ISSN 2520-1158
Abstract
The asymmetric reductive amination of ketones enables the one-step synthesis of chiral amines from readily available starting materials. Here we report the discovery of a family of native NAD(P)H-dependent Amine Dehydrogenases (nat-AmDHs) competent for the asymmetric reductive amination of aliphatic and alicyclic ketones, adding significantly to the biocatalytic toolbox available for chiral amine synthesis. Studies of ketone and amine substrate specificity and kinetics reveal a strong preference for aliphatic ketones and aldehydes, with activities of up to 614.5 mU mg-1 for cyclohexanone with ammonia and 851.3 mU mg-1 for isobutyraldehyde with methylamine as amine donor. Crystal structures of three nat-AmDHs (AmDH4, MsmeAmDH and CfusAmDH) reveal the active site determinants of substrate and cofactor specificity and enable the rational engineering of AmDH4 for generated activity towards pentan-2-one. Analysis of the 3D-catalytic site distribution among bacterial biodiversity revealed a superfamily of divergent proteins with representative specificities ranging from amino acid substrates to hydrophobic ketones.
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Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | 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: | 20 Mar 2019 09:30 |
Last Modified: | 02 Apr 2025 23:15 |
Published Version: | https://doi.org/10.1038/s41929-019-0249-z |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41929-019-0249-z |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:143845 |
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