A Manufactured Enzyme for the Synthesis of Chiral Amines

Significance

The authors report a biocatalytic transaminase (TA) mediated amination of ketones, specifically designed for the asymmetric synthesis of sitagliptin, a powerful antidiabetic β-aminoamide. Since the originally intended transaminases showed only poor activity for the desired transformations, systematic mutations of the target enzyme led to powerful TA libraries, capable of catalyzing various, formerly unknown aminations. The directed enzyme evolution was chosen in combination with in silico design studies. This strategy allowed a three-dimensional simulation of the chiral pocket, and thus an effective optimization of the structural properties needed for the ideal, desired reactivity of the developed enzyme.