Ducrot, Laurine, Bennett, Megan, Caparco, Adam et al. (5 more authors) (2021) Biocatalytic reductive amination by native Amine Dehydrogenases to access short chiral alkyl amines and amino alcohols. Frontiers in Catalysis. 781284. ISSN 2673-7841
Abstract
Small optically active molecules, and more particularly short-chain chiral amines, are key 20 compounds in the chemical industry and precursors of various pharmaceuticals. Their chemo-21 biocatalytic production on a commercial scale is already established, mainly through lipase-22 catalyzed resolutions leading to ChiProsTM products among others. Nevertheless, their 23 biocatalytic synthesis still remains challenging for very short-chain C4 to C5 amines due to low 24 enantiomeric excess. To complement the possibilities recently offered by transaminases, this 25 work describes alternative biocatalytic access using amine dehydrogenases (AmDHs). Without 26 any protein engineering, some of the already described wild-type AmDHs (CfusAmDH, 27 MsmeAmDH, MicroAmDH and MATOUAmDH2) were shown to be efficient for the synthesis 28 of hydroxylated or unfunctionalized small 2-aminoalkanes. Conversions up to 97.1% were 29 reached at 50 mM, and moderate to high enantioselectivities were obtained, especially for (S)-30 1-methoxypropan-2-amine (98.1%), (S)-3-aminobutan-1-ol (99.5%), (3S)-3-aminobutan-2-ol 31 (99.4%) and the small (S)-butan-2-amine (93.6%) with MsmeAmDH. Semi-preparative scale 32 up experiments were successfully performed at 150 mM substrate concentrations for the 33 synthesis of (S)-butan-2-amine and (S)-1-methoxypropan-2-amine, the latter known as “(S)-34 MOIPA”. Modelling studies provided some preliminary results explaining the basis for the 35 challenging discrimination between similarly sized substituents in the active sites of these 36 enzymes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 Ducrot, Bennett, Caparco, Champion, Bommarius, Zaparucha, Grogan and Vergne-Vaxelaire. |
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: | 26 Nov 2021 11:00 |
Last Modified: | 19 Dec 2024 00:13 |
Published Version: | https://doi.org/10.3389/fctls.2021.781284 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.3389/fctls.2021.781284 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:180890 |