A Role for Coenzyme M (2-mercaptoethanesulfonic Acid) in a Bacterial Pathway of Aliphatic Epoxide Carboxylation

Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8432-7. doi: 10.1073/pnas.96.15.8432.

Abstract

The bacterial metabolism of short-chain aliphatic alkenes occurs via oxidation to epoxyalkanes followed by carboxylation to beta-ketoacids. Epoxyalkane carboxylation requires four enzymes (components I-IV), NADPH, NAD(+), and a previously unidentified nucleophilic thiol. In the present work, coenzyme M (2-mercaptoethanesulfonic acid), a compound previously found only in the methanogenic Archaea where it serves as a methyl group carrier and activator, has been identified as the thiol and central cofactor of aliphatic epoxide carboxylation in the Gram-negative bacterium Xanthobacter strain Py2. Component I catalyzed the addition of coenzyme M to epoxypropane to form a beta-hydroxythioether, 2-(2-hydroxypropylthio)ethanesulfonate. Components III and IV catalyzed the NAD(+)-dependent stereoselective dehydrogenation of R- and S-enantiomers of 2-(2-hydroxypropylthio)ethanesulfonate to form 2-(2-ketopropylthio)ethanesulfonate. Component II catalyzed the NADPH-dependent cleavage and carboxylation of the beta-ketothioether to form acetoacetate and coenzyme M. These findings evince a newfound versatility for coenzyme M as a carrier and activator of alkyl groups longer in chain-length than methane, a function for coenzyme M in a catabolic pathway of hydrocarbon oxidation, and the presence of coenzyme M in the bacterial domain of the phylogenetic tree. These results serve to unify bacterial and Archaeal metabolism further and showcase diverse biological functions for an elegantly simple organic molecule.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkenes / metabolism
  • Archaea / enzymology
  • Carbon Isotopes
  • Carboxy-Lyases / metabolism*
  • Epoxy Compounds / metabolism
  • Gram-Negative Bacteria / enzymology
  • Gram-Negative Bacteria / metabolism*
  • Hydrocarbons / metabolism
  • Magnetic Resonance Spectroscopy
  • Mesna / metabolism*
  • Methyltransferases / metabolism
  • NAD / metabolism
  • NADP / metabolism
  • Propane / analogs & derivatives
  • Stereoisomerism
  • Sulfhydryl Compounds / chemistry

Substances

  • Alkenes
  • Carbon Isotopes
  • Epoxy Compounds
  • Hydrocarbons
  • Sulfhydryl Compounds
  • NAD
  • NADP
  • Methyltransferases
  • Carboxy-Lyases
  • epoxide carboxylase
  • Mesna
  • Propane