Isolation and Synthesis of One of the Most Central Cofactors in Metabolism: Coenzyme A

The isolation and synthesis of coenzyme A (CoA) has been an important field since this cofactor was discovered in 1947. CoA plays a central role in human metabolism and is vital in several metabolic pathways, including fatty acid transport and degradation as well as the biosynthesis of a wide variety of compounds, including fatty acids. The high cost of commercially available CoA ($2600/g with >85% purity) has motivated several research groups to find alternatives for its production. The variety of strategies that have been investigated for CoA production can be divided in three categories: isolation from microorganisms, total chemical synthesis, and chemoenzymatic synthesis. These approaches provide access to CoA with different efficiencies. For example, direct isolation yields of ∼25 mg/kg from dried yeast have been obtained. A variety of microorganisms such as Pseudomonas alkalytica, Sarcina lutea, and Brevibacterium ammoniagenes accumulate CoA in their cultures at levels ranging from 0.03 to 115 mg/mL. Total chemical synthesis yields have ranged between 25 and 54%, and chemoenzymatic approaches have provided overall yields of ca. 73%. This review covers all published works on producing CoA in order to compare their efficiencies, scalabilities, and convenience.