Bennett, Megan, Ducrot, Laurine, Vergne-Vaxelaire, Carine et al. (1 more author) (2022) Structure and Mutation of the Native Amine Dehydrogenase MATOUAmDH2. Chembiochem. e202200136. ISSN 1439-7633
Abstract
Native Amine Dehydrogenases (nat-AmDHs) have recently emerged as a potentially valuable new reservoir of enzymes for the sustainable and selective synthesis of chiral amines, catalyzing the NAD(P)H-dependent ammoniation of carbonyl compounds with high activity and selectivity. MATOUAmDH2, recently identified from the Marine Atlas of Tara Oceans Unigenes (MATOUv1) database of eukaryotic genes, displays exceptional catalytic performance against its best identified substrate, isobutyraldehyde, as well as broader substrate scope than other nat-AmDHs. In the interests of providing a platform for the rational engineering of this and other nat-AmDHs, we have determined the structure of MATOUAmDH2 in complex with NADP+ and also with the cofactor and cyclohexylamine. Monomers within the structure are representative of more open and closed conformations of the enzyme and illustrate the profound changes undergone by nat-AmDHs during the catalytic cycle. An alanine screen of active site residues revealed that M215A and L180A are more active than the wild-type enzyme for the amination of cyclohexanone with ammonia and methylamine respectively, the latter suggesting that AmDHs have the potential to be engineered for the improved production of secondary amines.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Authors. ChemBioChem published by Wiley-VCHGmbHWileyVC. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Funding Information: | Funder Grant number BBSRC (BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL) BB/T017805/1 |
Depositing User: | Pure (York) |
Date Deposited: | 04 Apr 2022 16:30 |
Last Modified: | 07 Jan 2025 12:20 |
Published Version: | https://doi.org/10.1002/cbic.202200136 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1002/cbic.202200136 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:185432 |
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