By the same authors

From the same journal

From the same journal

From the same journal

Multifunctional biocatalyst for conjugate reduction and reductive amination

Research output: Contribution to journalArticlepeer-review

Published copy (DOI)

Author(s)

  • Thomas Thorpe
  • James Marshall
  • Vanessa Harawa
  • Rebecca Ruscoe
  • Anibal Cuetos
  • James Finnigan
  • Antonio Angelastro
  • Rachel Heath
  • Fabio Parmeggianni
  • S.J. Charnock
  • Roger Howard
  • Rajesh Kumar
  • David Daniels
  • Gideon James Grogan
  • Nicholas Turner

Department/unit(s)

Publication details

JournalNature
DateAccepted/In press - 20 Jan 2022
DateE-pub ahead of print - 6 Apr 2022
DatePublished (current) - 2022
Volume604
Pages (from-to)86-91
Early online date6/04/22
Original languageEnglish

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.

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