Modular Enzymatic Cascade Synthesis of Vitamin B(5) and Its Derivatives

Access to vitamin B(5) [(R)‐pantothenic acid] and both diastereoisomers of α‐methyl‐substituted vitamin B(5) [(R)‐ and (S)‐3‐((R)‐2,4‐dihydroxy‐3,3‐dimethylbutanamido)‐2‐methylpropanoic acid] was achieved using a modular three‐step biocatalytic cascade involving 3‐methylaspartate ammonia lyase (MAL), aspartate‐α‐decarboxylase (ADC), β‐methylaspartate‐α‐decarboxylase (CrpG) or glutamate decarboxylase (GAD), and pantothenate synthetase (PS) enzymes. Starting from simple non‐chiral dicarboxylic acids (either fumaric acid or mesaconic acid), vitamin B(5) and both diastereoisomers of α‐methyl‐substituted vitamin B(5), which are valuable precursors for promising antimicrobials against Plasmodium falciparum and multidrug‐resistant Staphylococcus aureus, can be generated in good yields (up to 70 %) and excellent enantiopurity (>99 % ee). This newly developed cascade process may be tailored and used for the biocatalytic production of various vitamin B(5) derivatives by modifying the pantoyl or β‐alanine moiety.