Structural basis for a highly (S)-enantioselective reductase towards aliphatic ketones with only one carbon difference between side chain

Afifa Ayu Koesoema, Yosuke Sugiyama, Zichang Xu, Daron M. Standley, Miki Senda, Toshiya Senda, Tomoko Matsuda

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Aliphatic ketones, such as 2-butanone and 3-hexanone, with only one carbon difference among side chains adjacent to the carbonyl carbon are difficult to be reduced enantioselectively. In this study, we utilized an acetophenone reductase from Geotrichum candidum NBRC 4597 (GcAPRD) to reduce challenging aliphatic ketones such as 2-butanone (methyl ethyl ketone) and 3-hexanone (ethyl propyl ketone) to their corresponding (S)-alcohols with 94% ee and > 99% ee, respectively. Through crystallographic structure determination, it was suggested that residue Trp288 limit the size of the small binding pocket. Docking simulations imply that Trp288 plays an important role to form a C-H⋯π interaction for proper orientation of ketones in the pro-S binding pose in order to produce (S)-alcohols. The excellent (S)-enantioselectivity is due to a non-productive pro-R binding pose, consistent with the observation that the (R)-alcohol acts as an inhibitor of (S)-alcohol oxidation.

Original languageEnglish
Pages (from-to)9543-9553
Number of pages11
JournalApplied Microbiology and Biotechnology
Volume103
Issue number23-24
DOIs
Publication statusPublished - Dec 1 2019
Externally publishedYes

Keywords

  • Alcohol dehydrogenase
  • Asymmetric reduction
  • Crystal structure
  • Docking simulation
  • Enantioselectivity

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

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