By the same authors

Biocatalytic reductive amination by native Amine Dehydrogenases to access short chiral alkyl amines and amino alcohols

Research output: Contribution to journalArticlepeer-review

Full text download(s)

Published copy (DOI)

Author(s)

  • Gideon James Grogan
  • Megan Bennett
  • Laurine Ducrot
  • Carine Vergne-Vaxelaire
  • Anne Zaparucha
  • Andreas Bommarius
  • Adam Caparco
  • Julie Champion

Department/unit(s)

Publication details

JournalFrontiers in Catalysis
DateAccepted/In press - 29 Oct 2021
DatePublished (current) - 26 Nov 2021
Original languageEnglish

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.

Bibliographical note

© 2021 Ducrot, Bennett, Caparco, Champion, Bommarius, Zaparucha, Grogan and Vergne-Vaxelaire.

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations