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, has been engineered to accept NADH as a cofactor. The engineered TeSADH shows a >10,000-fold switch from NADPH towards NADH compared to the wild type enzyme. This TeSADH variant has been applied to a biocatalytic hydrogen borrowing system that employs catalytic amounts of NAD+, ammonia and an amine dehydrogenase (AmDH) thereby enabling the conversion a range of alcohols into chiral amines.