ketoacylreductase

Ketoacyl-ACP reductase, commonly called beta-ketoacyl-ACP reductase (KAR), is an enzyme in fatty acid biosynthesis. It catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP to beta-hydroxyacyl-ACP, a key step in the elongation cycle of type II fatty acid synthase systems found in bacteria, plants, and some fungi.

Mechanistically, KAR belongs to the short-chain dehydrogenase/reductase (SDR) superfamily and uses NADPH as the electron donor. It recognizes the ACP-bound beta-ketoacyl substrate and reduces the carbonyl group to a hydroxyl group, producing beta-hydroxyacyl-ACP. The product is subsequently dehydrated and reduced in downstream steps to continue fatty acid chain elongation. In most FAS II systems, substrates are ACP-tethered, though related pathways in polyketide biosynthesis may use analogous acyl carrier protein or CoA-linked substrates.

Genetics and structure vary by organism. In bacteria, the fabG gene encodes KAR; many species carry one or more paralogs. The enzyme commonly forms oligomers, often as a homotetramer, and features the Rossmann-like fold typical of SDR enzymes. It contains conserved catalytic tyrosine and lysine residues essential for activity.

Importance and applications: KAR is essential for cellular fatty acid synthesis, linking to membrane lipid formation and energy metabolism. Its inhibition can suppress lipid production, making it a potential target for antibiotics and antimicrobial development. In biotechnology, KAR activity is leveraged in metabolic engineering to optimize fatty acid or polyketide production and to study the regulation of lipid biosynthesis in different organisms.