Facile Stereoselective Reduction of Prochiral Ketones by using an F420 -dependent Alcohol Dehydrogenase

Chembiochem. 2021 Jan 5;22(1):156-159. doi: 10.1002/cbic.202000651. Epub 2020 Oct 23.

Abstract

Effective procedures for the synthesis of optically pure alcohols are highly valuable. A commonly employed method involves the biocatalytic reduction of prochiral ketones. This is typically achieved by using nicotinamide cofactor-dependent reductases. In this work, we demonstrate that a rather unexplored class of enzymes can also be used for this. We used an F420 -dependent alcohol dehydrogenase (ADF) from Methanoculleus thermophilicus that was found to reduce various ketones to enantiopure alcohols. The respective (S) alcohols were obtained in excellent enantiopurity (>99 % ee). Furthermore, we discovered that the deazaflavoenzyme can be used as a self-sufficient system by merely using a sacrificial cosubstrate (isopropanol) and a catalytic amount of cofactor F420 or the unnatural cofactor FOP to achieve full conversion. This study reveals that deazaflavoenzymes complement the biocatalytic toolbox for enantioselective ketone reductions.

Keywords: Biocatalysis; deazaflavin; enantioselectivity; prochiral ketones; reduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Dehydrogenase / chemistry
  • Alcohol Dehydrogenase / metabolism*
  • Alcohols / chemistry
  • Alcohols / metabolism*
  • Ketones / chemistry
  • Ketones / metabolism*
  • Methanomicrobiaceae / enzymology
  • Molecular Structure
  • Oxidation-Reduction
  • Stereoisomerism

Substances

  • Alcohols
  • Ketones
  • Alcohol Dehydrogenase