COA-Dependent Enzymes, Chemistry of

Coenzyme A (CoA) and its thioesters play a diverse array of roles in biologic systems. The enzymes that catalyze reactions of CoA are of interest for a variety of reasons, including, but not limited to, their potential as drug targets. The enzymology of CoA biosynthesis is now well understood, and the genes for all of the enzymes involved have been identified. Thioesters are inherently reactive toward acyl transfer reactions and toward reactions involving deprotonation of the α-carbon, and these are the primary reactivity patterns in enzyme-catalyzed reactions of CoA thioesters. CoA utilizing enzymes have been widely studied mechanistically and structurally. Analogs of the natural CoA thioester substrates have been widely used in these studies, including thioesters of unnatural or uncommon acyl groups as well as a large number of analogs in which the thioester is replaced with alternative functionality. Recent technical applications of CoA have included the tagging of carrier protein domains and carrier protein fusions with tagged phosphopantetheine derivatives transferred enzymatically from the corresponding tagged CoA derivatives using promiscuous phosphopantetheinyl transferases.