A High Yield Method for the Preparative Synthesis of Coenzyme A by Combination of Chemical and Enzymic Reactions

Dried cells of Brevibacterium ammoniagenes are a good enzyme source for the preparative synthesis of CoA from pantothenic acid, L-cysteine and ATP. A problem with this synthesis is that the CoA synthesis is repressed by negative feedback inhibition by CoA to pantothenate kinase, the first step enzyme for the biosynthesis of CoA, which catalyses phosphorylation of pantothenic acid or pantetheine. As the inhibition operates only at this step, a further increased yield is possible if the enzymic phosphorylation step is replaced with chemical synthesis. Yields from phosphorylated substrates are more than 10-times higher than those from pantothenic acid or pantetheine (33 g/l from phosphopantothenic acid with a molar yield of 86%; 115 g/l from phosphopantetheine with a molar yield of 100%).