A role for coenzyme M (2-mercaptoethanesulfonic acid) in a bacterial pathway of aliphatic epoxide carboxylation.
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.
Allen
J R
JR
Department of Chemistry and Biochemistry, Utah State University, Logan, UT 84322-0300, USA.
Clark
D D
DD
Krum
J G
JG
Ensign
S A
SA
D000475:Alkenes / Q000378:metabolism; D001105:Archaea / Q000201:enzymology; D002247:Carbon Isotopes; D002262:Carboxy-Lyases / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000201:enzymology / Q000378:metabolism*; D006838:Hydrocarbons / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015080:Mesna / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D011407:Propane / Q000031:analogs & derivatives; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000475:Alkenes; D002247:Carbon Isotopes; D004852:Epoxy Compounds; D006838:Hydrocarbons; D013438:Sulfhydryl Compounds; D009243:NAD; D009249:NADP; D008780:Methyltransferases; D002262:Carboxy-Lyases; C109739:epoxide carboxylase; D015080:Mesna; D011407:Propane