Stereoselective reduction of aromatic ketones by a new ketoreductase from Pichia glucozyma

Appl Microbiol Biotechnol. 2016 Jan;100(1):193-201. doi: 10.1007/s00253-015-6961-y. Epub 2015 Sep 16.

Abstract

A new NADPH-dependent benzil reductase (KRED1-Pglu) was identified from the genome of the non-conventional yeast Pichia glucozyma CBS 5766 and overexpressed in E. coli. The new protein was characterised and reaction parameters were optimised for the enantioselective reduction of benzil to (S)-benzoin. A thorough study of the substrate range of KRED1-Pglu was conducted; in contrast to most other known ketoreductases, KRED1-Pglu prefers space-demanding substrates, which are often converted with high stereoselectivity. A molecular modelling study was carried out for understanding the structural determinants involved in the stereorecognition experimentally observed and unpredictable on the basis of steric properties of the substrates. As a result, a new useful catalyst was identified, enabling the enantioselective preparation of different aromatic alcohols and hydroxyketones.

Keywords: Biocatalysis; Carbonyl reductase; Enantioselective reduction; Ketoreductase; Pichia glucozyma; Stereoselective.

MeSH terms

  • Alcohol Oxidoreductases / genetics*
  • Alcohol Oxidoreductases / metabolism*
  • Cloning, Molecular
  • Coenzymes / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Hydrocarbons, Aromatic / metabolism*
  • Ketones / metabolism*
  • Models, Molecular
  • NADP / metabolism
  • Pichia / enzymology*
  • Pichia / genetics*
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Coenzymes
  • Hydrocarbons, Aromatic
  • Ketones
  • NADP
  • Alcohol Oxidoreductases
  • benzil reductase