Biotransformation of β-keto nitriles to chiral (S)-β-amino acids using nitrilase and ω-transaminase

Abstract

Objective: To enzymatically synthesize enantiomerically pure β-amino acids from β-keto nitriles using nitrilase and ω-transaminase.

Results: An enzyme cascade system was designed where in β-keto nitriles are initially hydrolyzed to β-keto acids using nitrilase from Bradyrhizobium japonicum and subsequently β-keto acids were converted to β-amino acids using ω-transaminases. Five different ω-transaminases were tested for this cascade reaction, To enhance the yields of β-amino acids, the concentrations of nitrilase and amino donor were optimized. Using this enzymatic reaction, enantiomerically pure (S)-β-amino acids (ee > 99%) were generated. As nitrilase is the bottleneck in this reaction, molecular docking analysis was carried out to depict the poor affinity of nitrilase towards β-keto acids.

Conclusions: A novel enzymatic route to generate enantiomerically pure aromatic (S)-β-amino acids from β-keto nitriles is demonstrated for the first time.

Keywords: Asymmetric synthesis; Molecular docking; Nitrilase; β-Amino acids; β-Keto acids; β-Keto nitriles; ω-Transaminase.