The biosynthesis of coenzyme A in bacteria.
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.
Begley
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TP
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, USA.
Kinsland
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C
Strauss
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E
D003065:Coenzyme A / Q000096:biosynthesis*; D003653:Decarboxylation; D004926:Escherichia coli / Q000201:enzymology*; D006801:Humans; D010084:Oxidation-Reduction; D010205:Pantothenic Acid / Q000008:administration & dosage / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*
D010205:Pantothenic Acid; D003065:Coenzyme A