ketoreductase

Ketoreductase (KR) refers to an enzymatic activity that reduces a beta-keto group to a beta-hydroxy group during the biosynthesis of fatty acids and related polyketide compounds. In type II fatty acid synthase (FAS II) systems, the beta-ketoacyl-ACP reductase step converts beta-ketoacyl-ACP to beta-hydroxyacyl-ACP, a key elongated intermediate in cycles of chain elongation. In modular and iterative polyketide synthases (PKS), KR domains perform a similar reduction on beta-ketoacyl-ACP substrates, contributing to the stereochemistry and oxidation state of the resulting polyketide units.

Biochemically, ketoreductases typically utilize NADPH as an electron donor to deliver a hydride to the carbonyl carbon. Many characterized KRs belong to the short-chain dehydrogenase/reductase (SDR) superfamily and share common catalytic features that facilitate hydride transfer and protonation. The enzymes can exhibit substrate specificity for chain length, substitution pattern, and the configuration of the resulting hydroxyl group, thereby influencing the stereochemistry of the product.

Distribution and role: KR activity is found across bacteria, plants, and fungi, reflecting its central function in fatty acid biosynthesis and the diversification of polyketide metabolites. In fatty acid synthesis, KR activity helps determine the properties of the growing acyl chain, while in PKS pathways it contributes to the structural diversity of natural products.

Applications: Understanding and engineering KR domains is of interest in metabolic engineering and natural product biosynthesis, where altering KR specificity or stereochemical outcome can shift product profiles toward desired fatty acids or polyketide scaffolds.