Generation of oxidoreductases with dual alcohol dehydrogenase and amine dehydrogenase activity.

Generation of oxidoreductases with dual alcohol dehydrogenase and amine dehydrogenase activity.
Chemistry. 2020 Oct 19;:
Authors: Tseliou V, Schilder D, Masman MF, Knaus T, Mutti F
Abstract
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 sa...

Source: Chemistry - October 19, 2020 Category: Chemistry Authors: Tseliou V, Schilder D, Masman MF, Knaus T, Mutti F Tags: Chemistry Source Type: research