Discovery of arylmalonate decarboxylase and conversion of the function by rational design

Decarboxylation of malonic acid is a well-known process in the biosynthesis of long-chain fatty acids starting from acetic acid. If this kind of enzymes exhibits enantioselectivity for asubstituted malonates, it will be useful as a novel method for preparing optically active carboxylic acids. Indeed malonyl-CoA decarboxylase from uropygial gland is enantioselective to the substrate and the product. Racemate of methylmalonyl-CoA (1) was incubated with the above decarboxylase in ³H₂O. (S)-Enantiomer was smoothly decarboxylated to result in 2-(³H)-propionyl-CoA (2), while (R)-isomer of the substrate remained intact (Equation 21.1). The absolute configuration of α-carbon of resulting 2 was revealed to be (R). Thus, the decarboxylase distinguishes the chirality of 1 and gives enantiomerically pure (R)-isomer by retention of configuration [1].