Alcohol‐dehydrogenase‐catalyzed production of chiral hydrophobic alcohols. A new approach leading to a nearly waste‐free process

The enantioselective enzyme‐catalyzed reduction of ketones in an enzyme membrane reactor coupled to a membrane‐based extractive product separation was developed for the production of chiral hydrophobic alcohols. Enantiomerically pure (S)‐1‐phenylpropan‐2‐ol, (S)‐4‐phenylbutan‐2‐ol and (S)‐6‐methylhept‐5‐en‐2‐ol (sulcatol) were obtained with high purities. In spite of low substrate concentrations (9‐12 mM) space‐time yields higher than 100 g/(l·d) and concentrated product solutions were obtained. Formate‐dehydrogenase‐catalyzed regeneration of cofactor, together with process‐integrated recycling of cofactor, led to total‐turnover numbers for NAD+ of up to 1350 molP/molNAD, which means a 25‐fold increase in comparison with standard techniques without cofactor retention. Because of the closed‐loop design of the reactor the process can be run almost without waste, yielding the pure chiral alcohol and CO2.