March 2021: Hot Paper on ‘alcohol aminase’ enzymes is cover feature of Chemistry–A European Journal

Our research features on the cover of Chemistry–A European Journal. The “Hot Paper” reports on the generation of oxidoreductases that possess both alcohol dehydrogenase and amine dehydrogenase activity. This opens up new opportunities in biocatalytic organic synthesis.


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.


Vasilis Tseliou, Don Schilder, Marcelo F. Masman, Tanja Knaus, Francesco G. Mutti: Generation of Oxidoreductases with Dual Alcohol Dehydrogenase and Amine Dehydrogenase Activity Chem. Eur. J. 10/2021. Paper: DOI 10.1002/chem.202003140 Cover feature: DOI 10.1002/chem.202004194

The paper is part of the “Young Chemists 2020” special collection of Chemistry, A European Journal.