Stairway to Stereoisomers: Engineering Short‐ and Medium‐Chain Ketoreductases To Produce Chiral Alcohols

Abstract The short‐ and medium‐chain dehydrogenase/reductase superfamilies are responsible for most chiral alcohol production in laboratories and industries. In nature, they participate in diverse roles such as detoxification, housekeeping, secondary metabolite production, and catalysis of several chemicals with commercial and environmental significance. As a result, they are used in industries to create biopolymers, active pharmaceutical intermediates (APIs), and are also used as components of modular enzymes like polyketide synthases for fabricating bioactive molecules. Consequently, random, semi‐rational and rational engineering have helped transform these enzymes into product‐oriented efficient catalysts. The rise of newer synthetic chemicals and their enantiopure counterparts has proved challenging, and engineering them has been the subject of numerous studies. However, they are frequently limited to the synthesis of a single chiral alcohol. The study attempts to defragment and describe hotspots of engineering short‐ and medium‐chain dehydrogenases/reductases for the production of chiral synthons.