Two-Enzyme Hydrogen-Borrowing Amination of Alcohols Enabled by a Cofactor-Switched Alcohol Dehydrogenase

The NADPH-dependent secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus (TeSADH), displaying broad substrate specificity and low enantioselectivity, was engineered to accept NADH as a cofactor. The engineered TeSADH showed a >10000-fold switch from NADPH towards NADH compared to the wildtype enzyme. This TeSADH variant was applied to a biocatalytic hydrogen-borrowing system that employed catalytic amounts of NAD(+), ammonia, and an amine dehydrogenase, which thereby enabled the conversion a range of alcohols into chiral amines.