Abstract

Biocatalysis has emerged as a transformative technology in pharmaceutical synthesis, enabling efficient and sustainable production of chiral bioactive compounds. This review focuses on recent advancements in biocatalytic methods, highlighting key enzyme systems, such as ketoreductases, aminotransferases, and imine reductases, which facilitate the synthesis of chiral alcohols, amines, and other pharmaceutical intermediates with high enantiomeric purity. Directed evolution and protein engineering have significantly enhanced enzyme stability, activity, and substrate specificity, broadening their applications in industrial-scale drug production. For example, ketoreductases have been successfully applied in the synthesis of intermediates for drugs, such as enalapril and duloxetine, while engineered transaminases enable efficient production of sitagliptin. Beyond asymmetric reduction and transamination, advancements in C-H bond activation using enzymes like P450 monooxygenases and unspecific peroxygenases provide new opportunities for regioselective functionalization. Additionally, multienzyme cascade reactions and chemo-biocatalytic approaches integrate multiple catalytic steps into single processes, reducing reaction complexity and waste while enhancing efficiency. These innovations highlight the growing role of biocatalysis in green chemistry, offering a sustainable alternative to traditional chemical synthesis methods. As the field advances with contributions from bioinformatics, artificial intelligence, and high-throughput techniques, biocatalysis is poised to drive further innovation in pharmaceutical manufacturing, fostering environmentally friendly processes and scalable solutions for complex drug synthesis. This review underscores the critical impact of biocatalysis in shaping the future of sustainable chemistry and its pivotal role in addressing the growing demand for greener pharmaceutical technologies.

Keywords: Chiral pharmaceuticals, biocatalytic reaction, multi-enzymatic cascade reaction, direct evolution, C-H activation