Biologics: Targets & Therapy (Jun 2024)
Enzymatic Routes for Chiral Amine Synthesis: Protein Engineering and Process Optimization
Abstract
Sayali Shantaram Vikhrankar,1 Seema Satbhai,2 Priyanka Kulkarni,2 Ranjit Ranbhor,3 Vibin Ramakrishnan,4 Prashant Kodgire1 1Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, MP, India; 2Sevit Healthcare Private Limited, Pune, MH, India; 3Pergament & Cepeda LLP, Florham Park, NJ, USA; 4Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, IndiaCorrespondence: Ranjit Ranbhor, Pergament & Cepeda LLP, 25A Hanover Road, Florham Park, NJ, 07932, USA, Tel +1 973 967 0490, Email [email protected]: Chiral amines are essential motifs in pharmaceuticals, agrochemicals, and specialty chemicals. While traditional chemical routes to chiral amines often lack stereoselectivity and require harsh conditions, biocatalytic methods using engineered enzymes can offer high efficiency and selectivity under sustainable conditions. This review discusses recent advances in protein engineering of transaminases, oxidases, and other enzymes to improve catalytic performance. Strategies such as directed evolution, immobilization, and computational redesign have expanded substrate scope and enhanced efficiency. Furthermore, process optimization guided by techno-economic assessments has been crucial for establishing viable biomanufacturing routes. Combining state-of-the-art enzyme engineering with multifaceted process development will enable scalable, economical enzymatic synthesis of diverse chiral amine targets.Keywords: chiral amines, biocatalysis, protein engineering, ω-transaminases, sitagliptin, enzyme immobilization, co-factor regeneration
