Unlocking the catalytic potential of transaminase: A two-decade evolution toward green and scalable biocatalysis

Over the past two decades, transaminases or aminotransferases have been involved in the chemoenzymatic synthesis of active pharmaceutical ingredients by highly efficient and straightforward catalysis of prochiral ketones to chiral amines. These enzymes are promising targets used in the pharmaceutical sector since they are relatively easy to clone and express from a variety of bacteria and other species, where they play key catalytic roles in amino acid metabolic pathways. Also, their high thermal and solvent stability makes them very suitable candidates for use in industry. These enzymes are selected based on their substrate specificity and catalytic efficiency, and are further evolved into industrial enzymes using protein engineering and enzyme recyclability methods. Their key catalytic role in APIs and pharmaceutical-relevant molecules synthesis involves asymmetric synthesis, kinetic resolution, and deracemization. Although these enzymes are now regularly used in industry for the synthesis of Sitagliptin, Mexiletine, Dolutegravir, etc., there is still scope for improvement involving challenges such as equilibrium thermodynamics, co-product removal, limited substrate tolerance, and scope. This review focuses on the detailed use of these enzymes in the pharmaceutical industry over the past 20 years and comprehensive approaches encompassing protein and equilibrium engineering, immobilization, continuous-flow biocatalysis, smart donors, and multi-enzymatic cascades, which have been and are being used for their evolution into the pharmaceutical industry.