Sequential Enzymatic Conversion of α-Angelica Lactone to γ-Valerolactone through Hydride-Independent C=C Bond Isomerization

ChemSusChem. 2016 Dec 20;9(24):3393-3396. doi: 10.1002/cssc.201601363. Epub 2016 Nov 25.

Abstract

A case of hydride-independent reaction catalyzed by flavin-dependent ene-reductases from the Old Yellow Enzyme (OYE) family was identified. α-Angelica lactone was isomerized to the conjugated β-isomer in a nicotinamide-free and hydride-independent process. The catalytic cycle of C=C bond isomerization appears to be flavin-independent and to rely solely on a deprotonation-reprotonation sequence through acid-base catalysis. Key residues in the enzyme active site were mutated and provided insight on important mechanistic features. The isomerization of α-angelica lactone by OYE2 in aqueous buffer furnished 6.3 mm β-isomer in 15 min at 30 °C. In presence of nicotinamide adenine dinucleotide (NADH), the latter could be further reduced to γ-valerolactone. This enzymatic tool was successfully applied on semi-preparative scale and constitutes a sustainable process for the valorization of platform chemicals from renewable resources.

Keywords: biobased chemicals; biocatalysis; ene-reductases; isomerization; α-angelica lactone.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemistry
  • Carbon / chemistry*
  • Catalytic Domain
  • Hydrogen / chemistry*
  • Isomerism
  • Lactones / chemistry*
  • Oxidoreductases / chemistry
  • Oxidoreductases / metabolism*
  • Temperature

Substances

  • Lactones
  • angelica lactone
  • Carbon
  • Hydrogen
  • Oxidoreductases
  • gamma-valerolactone
  • 4-Butyrolactone