The Substrate Spectrum of Mandelate Racemase: Minimum Structural Requirements for Substrates and Substrate Model

Mandelate racemase (EC 5.1.2.2) is one of the few biochemically well‐characterized racemases. The remarkable stability of this cofactor‐independent enzyme and its broad substrate tolerance make it an ideal candidate for the racemization of non‐natural α‐hydroxycarboxylic acids under physiological reaction conditions to be applied in deracemization protocols in connection with a kinetic resolution step. This review summarizes all aspects of mandelate racemase relevant for the application of this enzyme in preparative‐scale biotransformations with special emphasis on its substrate tolerance. Collection and evaluation of substrate structure‐activity data led to a set of general guidelines, which were used as basis for the construction of a general substrate model, which allows a quick estimation of the expected activity for a given substrate.