ketoreduktaser

Ketoreductases, or KREDs, are enzymes that catalyze the enantioselective reduction of ketones to secondary alcohols. They are found in bacteria, fungi, and plants and are widely used in biocatalysis to produce chiral building blocks for pharmaceuticals and fine chemicals. In nature, they participate in carbonyl metabolism and detoxification pathways; in industry, they enable asymmetric synthesis under mild conditions.

Typically, KREDs transfer a hydride from NAD(P)H to the carbonyl carbon and gain a proton from the solvent to form the alcohol. The reactions proceed under aqueous conditions and often at ambient temperatures, delivering high stereoselectivity that can be difficult to achieve with conventional chemistry. Substrate scope varies by enzyme; common substrates include acetophenones, cyclohexanone derivatives, and various aryl- and alkyl-substituted ketones. The stereochemical outcome depends on the enzyme; some KREDs preferentially give (R)-secondary alcohols, others (S)-enantiomers.

Most KREDs belong to the short-chain dehydrogenase/reductase (SDR) superfamily, characterized by a Rossmann-type fold for NAD(P)H binding and a conserved catalytic motif often including a Tyr–Lys pair. Other families, such as aldo-keto reductases (AKRs), also provide ketoreductases with distinct active sites. Cofactor recycling systems, such as glucose dehydrogenase or formate dehydrogenase, are commonly used to sustain NAD(P)H supply and reduce cost.

Industrial use and engineering: KREDs are central to the production of chiral alcohols and pharmaceutical intermediates. They can be used in whole cells or as purified enzymes, and may be immobilized for reuse. Protein engineering and enzyme discovery continue to broaden substrate scope and improve stability and performance.