Unlocking the industrial potential of ketoreductase: insights from two decades of discovery, evolution, and global impact.

The increasing demand for sustainable and cost-effective manufacturing routes has positioned ketoreductases (KREDs) at the forefront of industrial biocatalysis. As one of the most widely applied classes of oxidoreductases in asymmetric synthesis, KREDs provide high enantioselectivity and operational simplicity under mild reaction conditions. These enzymes catalyze the asymmetric reduction of ketones to chiral alcohols molecules central to pharmaceuticals, fine chemicals, and agrochemical and fragrance industries while ensuring minimal environmental impact. This review provides a comprehensive overview of KRED discovery, natural diversity, and evolutionary classification, substrate selectivity, and structural diversity analyses. We discuss substrate scope, stereochemical preferences, and adaptability toward both short- and long-chain carbonyl compounds. Recent advancements in enzyme engineering, including directed evolution, rational design, and high-throughput screening technologies, are examined in the context of improving catalytic efficiency, stability, and substrate tolerance for large-scale applications. Moreover, the industrial significance of KREDs is analysed with reference to global API market trends, and industrial landscaping of KRED applications and growth trends in the biocatalyst market. Despite their success, limitations such as cofactor recycling and process scalability remain challenges for widespread adoption. The review concludes with a forward-looking perspective on the integration of KREDs in sustainable biomanufacturing and industrial-scale green chemistry.