Flavin-N5 Covalent Intermediate in a Nonredox Dehalogenation Reaction Catalyzed by an Atypical Flavoenzyme

Chembiochem. 2018 Jan 4;19(1):53-57. doi: 10.1002/cbic.201700594. Epub 2017 Dec 12.

Abstract

The flavin-dependent enzyme 2-haloacrylate hydratase (2-HAH) catalyzes the conversion of 2-chloroacrylate, a major component in the manufacture of acrylic polymers, to pyruvate. The enzyme was expressed in Escherichia coli, purified, and characterized. 2-HAH was shown to be monomeric in solution and contained a non-covalent, yet tightly bound, flavin adenine dinucleotide (FAD). Although the catalyzed reaction was redox-neutral, 2-HAH was active only in the reduced state. A covalent flavin-substrate intermediate, consistent with the flavin-acrylate iminium ion, was trapped with cyanoborohydride and characterized by mass spectrometry. Small-angle X-ray scattering was consistent with 2-HAH belonging to the succinate dehydrogenase/fumarate reductase family of flavoproteins. These studies establish 2-HAH as a novel noncanonical flavoenzyme.

Keywords: covalent adduct; dehalogenation; flavin; iminium adduct; non-redox reactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biocatalysis
  • Escherichia coli / metabolism
  • Flavin-Adenine Dinucleotide / metabolism
  • Flavins / chemistry
  • Flavins / metabolism*
  • Flavoproteins / genetics
  • Flavoproteins / metabolism*
  • Halogenation
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism
  • Kinetics
  • Mass Spectrometry
  • Scattering, Small Angle
  • X-Ray Diffraction

Substances

  • Flavins
  • Flavoproteins
  • Flavin-Adenine Dinucleotide
  • Hydro-Lyases