Characterization of imine reductases in reductive amination for the exploration of structure-activity relationships

Research output: Contribution to journalArticle

  • External authors:
  • Sarah Montgomery
  • Ahir Pushpanath
  • Rachel Heath
  • James Marshall
  • Ulrike Klemstein
  • James Galman
  • David Woodlock
  • Serena Bisagni
  • Christopher Taylor
  • Juan Mangas-Sanchez
  • Jeremy Ramsden
  • Beatriz Dominguez

Abstract

Imine reductases (IREDs) have shown great potential as catalysts for the asymmetric synthesis of industrially relevant chiral amines, but a limited understanding of sequence activity relationships makes rational engineering challenging. Here, we describe the characterization of 80 putative and 15 previously described IREDs across 10 different transformations and confirm that reductive amination catalysis is not limited to any particular subgroup or sequence motif. Furthermore, we have identified another dehydrogenase subgroup with chemoselectivity for imine reduction. Enantioselectivities were determined for the reduction of the model substrate 2-phenylpiperideine, and the effect of changing the reaction conditions was also studied for the reductive aminations of 1-indanone, acetophenone, and 4-methoxyphenylacetone. We have performed sequence-structure analysis to help explain clusters in activity across a phylogenetic tree and to inform rational engineering, which, in one case, has conferred a change in chemoselectivity that had not been previously observed.

Bibliographical metadata

Original languageEnglish
Pages (from-to)eaay9320
Number of pages13
JournalScience Advances
Volume6
Issue number21
DOIs
Publication statusPublished - 22 May 2020