title: Aliphatic epoxide carboxylation.
abstract: Aliphatic epoxides (epoxyalkanes) are highly reactive electrophilic molecules that are formed from the monooxygenase-catalyzed epoxidation of aliphatic alkenes. The bacterial metabolism of short-chain epoxyalkanes occurs by a three-step pathway resulting in net carboxylation to beta-ketoacids. This pathway uses the atypical cofactor coenzyme M (CoM; 2-mercaptoethanesulfonic acid) as the nucleophile for the epoxide ring opening and as the carrier of 2-hydroxyalkyl- and 2-ketoalkyl-CoM intermediates. Four enzymes are involved in epoxide carboxylation: a zinc-dependent alkyltransferase, two short-chain dehydrogenases with specificities for the chiral products of the R- and S-1,2-epoxyalkane ring opening, and an NADPH:disulfide oxidoreductase/carboxylase that reduces the thioether bond of the 2-ketoalkyl-CoM conjugate and carboxylates the resulting carbanion. In this review, we summarize the biochemical, mechanistic, and structural features of the enzymes of epoxide carboxylation and show how these enzymes, together with CoM, work in concert to achieve this highly unusual carboxylation reaction.
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, Logan, Utah 84322, USA. ensigns@cc.usu.edu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Ensign
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Allen
mesh_terms: D000475:Alkenes / Q000378:metabolism; D019883:Alkyl and Aryl Transferases / Q000737:chemistry / Q000378:metabolism*; D001419:Bacteria / Q000378:metabolism; D002262:Carboxy-Lyases / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism*; D015080:Mesna / Q000378:metabolism; D008958:Models, Molecular; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D004852:Epoxy Compounds; D009243:NAD; D009249:NADP; D010088:Oxidoreductases; D019883:Alkyl and Aryl Transferases; D002262:Carboxy-Lyases; D015080:Mesna