Rational design of the carbonyl reductase EbSDR8 for efficient biosynthesis of enantiopure (R)-3-chloro-1-phenyl-1-propanol

Computational Redesign of the Substrate Binding Pocket of Glutamate Dehydrogenase for Efficient Synthesis of Noncanonical l-Amino Acids

“…Compared with the natural substrate αKG, PPO and PBO have a larger side chain moiety, which might prevent them from being recognized and anchored by the substrate binding pocket. For bulky substrate molecules, reducing steric hindrance of the binding pocket is a common and effective engineering method to improve enzyme activity. − Molecular docking revealed the general position of substrates in the binding pocket of CdGluDH (Figure ), and eight amino acid residues within the range of 8 Å around the C5 atom of the natural substrate αKG were selected to be substituted with small-size amino acids including alanine and glycine (Figure A). Interestingly, three variants including A145G, P144A, and V143A showed significantly improved activities toward non-natural substrates (Figure B and Table S2).…”

Biotransamination with racemic amines as amine donors: kill three birds with one stone through a dual-enzyme cascade

“…This engineered carbonyl reductase, EbSDR8-G94A/S153L, is able to asymmetrically reduce a variety of substituted acetophenones, producing related chiral α-aromatic ethanols with remarkable ee without relying on NAD (P)H, instead utilizing the more affordable isopropanol as cosubstrate. 29,30 Acetophenones and α-ketoamides, both at a concentration of 2.5 mM, were mixed with EbSDR8-G94A/S153L, exhibiting specifically activity towards acetophenones instead of the α-ketoamides. It was anticipated that the reactivity of EbSDR8-G94A/S153L was expected to meet the requirements of selectively reducing substituted acetophenones, which are coproducts derived from (S)-or (R)-1-arylethylamines (amino donors).…”