The l‐lysine‐ϵ‐dehydrogenase (LysEDH) from Geobacillus stearothermophilus naturally catalyzes the oxidative deamination of the ϵ‐amino group of l‐lysine. We previously engineered this enzyme to create amine dehydrogenase (AmDH) variants that possess a new hydrophobic cavity in their active site such that aromatic ketones can bind and be converted into α‐chiral amines with excellent enantioselectivity. We also recently observed that LysEDH was capable of reducing aromatic aldehydes into primary alcohols. Herein, we harnessed the promiscuous alcohol dehydrogenase (ADH) activity of LysEDH to create new variants that exhibited enhanced catalytic activity for the reduction of substituted benzaldehydes and arylaliphatic aldehydes to primary alcohols. Notably, these novel engineered dehydrogenases also catalyzed the reductive amination of a variety of aldehydes and ketones with excellent enantioselectivity, thus exhibiting a dual AmDH/ADH activity. We envisioned that the catalytic bi‐functionality of these enzymes could be applied for the direct conversion of alcohols into amines. As a proof‐of‐principle, we performed an unprecedented one‐pot “hydrogen‐borrowing” cascade to convert benzyl alcohol to benzylamine using a single enzyme. Conducting the same biocatalytic cascade in the presence of cofactor recycling enzymes (i.e., NADH‐oxidase and formate dehydrogenase) increased the reaction yields. In summary, this work provides the first examples of enzymes showing “alcohol aminase” activity.

The catalytic promiscuity of LysEDH—which naturally catalyzes the oxidative deamination of l‐lysine at the ϵ‐amino group—was harnessed to create variants that exhibited alcohol dehydrogenase (ADH) and amine dehydrogenase (AmDH) activities. These ADH and AmDH activities could be switched by changing the reaction conditions. The dual ADH‐AmDH activity (i.e., alcohol aminase) was applied to convert benzyl alcohol to benzylamine using a single enzyme. The artwork illustrates a “water lever” that represents the switch of the enzyme's activity from an AmDH to an ADH and vice versa. More information can be found in the Full Paper by F. G. Mutti et al. on page 3315.