The biosynthesis of coenzyme A in bacteria

Abstract

Coenzyme A (I) and enzyme-bound phosphopantetheine (II) function as acyl carriers and as carbonyl activating groups for Claisen reactions as well as for amide-, ester-, and thioester-forming reactions in the cell. In so doing, these cofactors play a key role in the biosynthesis and breakdown of fatty acids and in the biosynthesis of polyketides and nonribosomal peptides. Coenzyme A is biosynthesized in bacteria in nine steps. The biosynthesis begins with the decarboxylation of aspartate to give beta-alanine. Pantoic acid is formed by the hydroxymethylation of alpha-ketoisovalerate followed by reduction. These intermediates are then condensed to give pantothenic acid. Phosphorylation of pantothenic acid followed by condensation with cysteine and decarboxylation gives 4'-phosphopantetheine. Adenylation and phosphorylation of 4'-phosphopantetheine completes the biosynthesis of coenzyme A. This review will focus on the mechanistic enzymology of coenzyme A biosynthesis in bacteria.