Biosynthesis of Pantothenic Acid and Coenzyme A

Pantothenate is vitamin B5 and is the key precursor for the biosynthesis of coenzyme A (CoA), a universal and essential cofactor involved in a myriad of metabolic reactions, including the synthesis of phospholipids, the synthesis and degradation of fatty acids, and the operation of the tricarboxylic acid cycle. CoA is also the only source of the phosphopantetheine prosthetic group for enzymes that shuttle intermediates between the active sites of enzymes involved in fatty acid, nonribosomal peptide, and polyketide synthesis. Pantothenate can be synthesized de novo and/or transported into the cell through a pantothenatepermease. Pantothenate uptake is essential for those organisms that lack the genes to synthesize this vitamin. The intracellular levels of CoA are controlled by the balance between synthesis and degradation. In particular, CoA is assembled in five enzymatic steps, starting from the phosphorylation of pantothenate to phosphopantothenatecatalyzed by pantothenate kinase, the product of the coaA gene. In some bacteria, the production of phosphopantothenate by pantothenate kinase is the rate limiting and most regulated step in the biosynthetic pathway. CoA synthesis additionally networks with other vitamin-associated pathways, such as thiamine and folic acid.