Quantum Chemical Study of Dual-Substrate Recognition in ω-Transaminase

ACS Omega
Bianca MantaFahmi Himo

Abstract

ω-Transaminases are attractive biocatalysts for the production of chiral amines. These enzymes usually have a broad substrate range. Their substrates include hydrophobic amines as well as amino acids, a feature referred to as dual-substrate recognition. In the present study, the reaction mechanism for the half-transamination of l-alanine to pyruvate in (S)-selective Chromobacterium violaceum ω-transaminase is investigated using density functional theory calculations. The role of a flexible arginine residue, Arg416, in the dual-substrate recognition is investigated by employing two active-site models, one including this residue and one lacking it. The results of this study are compared to those of the mechanism of the conversion of (S)-1-phenylethylamine to acetophenone. The calculations suggest that the deaminations of amino acids and hydrophobic amines follow essentially the same mechanism, but the energetics of the reactions differ significantly. It is shown that the amine is kinetically favored in the half-transamination of l-alanine/pyruvate, whereas the ketone is kinetically favored in the half-transamination of (S)-1-phenylethylamine/acetophenone. The calculations further support the proposal that the arginine residue fac...Continue Reading

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Citations

Mar 21, 2019·Frontiers in Molecular Biosciences·Jing LiangJianyong Li
Feb 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tolbert OsireZhiming Rao
Jan 29, 2020·ACS Chemical Biology·Moritz VossUwe T Bornscheuer

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Methods Mentioned

BETA
deamination

Software Mentioned

Gaussian09

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