Engineered Aminotransferase for the Production of <scp>d</scp>‐Phenylalanine Derivatives Using Biocatalytic Cascades

Abstract

Abstract d ‐Phenylalanine derivatives are valuable chiral building blocks for a wide range of pharmaceuticals. Here, we developed stereoinversion and deracemization biocatalytic cascades to synthesize d ‐phenylalanine derivatives that contain electron‐donating or ‐withdrawing substituents of various sizes and at different positions on the phenyl ring with a high enantiomeric excess (90 to &gt;99 % ee ) from commercially available racemic mixtures or l ‐amino acids. These whole‐cell systems couple Proteus mirabilis l ‐amino acid deaminase with an engineered aminotransferase that displays native‐like activity towards d ‐phenylalanine, which we generated from Bacillus sp. YM‐1 d ‐amino acid aminotransferase. Our cascades are applicable to preparative‐scale synthesis and do not require cofactor‐regeneration systems or chemical reducing agents.