Thorpe, Thomas, Marshall, James, Harawa, Vanessa et al. (12 more authors) (2022) Multifunctional biocatalyst for conjugate reduction and reductive amination. Nature. pp. 86-91. ISSN 0028-0836
Abstract
Chiral amine diastereomers are ubiquitous in pharmaceuticals and agrochemicals,1 yet their preparation often relies on low-efficiency multi-step synthesis.2 These valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of the molecule. Herein, we report the discovery and characterisation of a multi-functional biocatalyst for amine synthesis, which operates using a previously unreported mechanism. This enzyme (EneIRED), identified within a metagenomic imine reductase (IRED) collection3 and originating from an unclassified Pseudomonas species, possesses an unusual active site architecture that facilitates amine-activated conjugate alkene reduction followed by reductive amination. This enzyme can couple a broad selection of α,β-unsaturated carbonyls with amines for the efficient preparation of chiral amine diastereomers baring up to three stereocentres. Mechanistic and structural studies have been carried out to delineate the order of individual steps catalysed by EneIRED which have led to a proposal for the overall catalytic cycle. This work shows that the IRED family can serve as a platform for facilitating the discovery of further enzymatic activities for application in synthetic biology and organic synthesis.
Metadata
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) |
Funding Information: | Funder Grant number BBSRC (BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL) BB/T017805/1 |
Depositing User: | Pure (York) |
Date Deposited: | 19 Apr 2022 12:10 |
Last Modified: | 07 Feb 2025 00:32 |
Published Version: | https://doi.org/10.1038/s41586-022-04458-x |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41586-022-04458-x |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:185820 |