Aliphatic Epoxide Carboxylation

Abstract

▪ 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 β-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.