LAUSR

Alcohol dehydrogenase (ADH) and amine dehydrogenase (AmDH)‐catalyzed one‐pot cascade conversion of an alcohol to an amine provides a simple preparation of chiral amines. To enhance the cofactor recycling in this reaction, we report a new concept of coupling whole‐cells with the cell‐free system to enable separated intracellular and extracellular cofactor regeneration and recycling. This was demonstrated by the respective biotransformation of racemic 4‐phenyl‐2‐butanol 1a and 1‐phenyl‐2‐propanol 1b to (R)‐4‐phenylbutan‐2‐amine 3a and (R)‐1‐phenylpropan‐2‐amine 3b. Escherichia coli cells expressing S‐enantioselective CpsADH, R‐enantioselective PfODH, and NADH oxidase (NOX) was developed to oxidize racemic alcohols 1a–b to ketones 2a–b with full conversion via intracellular NAD+ recycling. AmDH and glucose dehydrogenase (GDH) were used to convert ketones 2a–b to amines (R)‐3a–b with 89–94% conversion and 891–943 times recycling of NADH. Combining the cells and enzymes for the cascade transformation of racemic alcohols 1a–b gave 70% and 48% conversion to the amines (R)‐3a and (R)‐3b in 99% ee, with a total turnover number (TTN) of 350 and 240 for NADH recycling, respectively. Improved results were obtained by using the E. coli cells with immobilized AmDH and GDH: (R)‐3a was produced in 99% ee with 71–84% conversion and a TTN of 1410‐1260 for NADH recycling, the highest value so far for the ADH–AmDH‐catalyzed cascade conversion of alcohols to amines. The concept might be generally applicable to this type of reactions.