fabG

FabG, short for beta-ketoacyl-ACP reductase, is an enzyme of the type II fatty acid synthase (FAS II) pathway in bacteria and in plastids of plants. It catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP to beta-hydroxyacyl-ACP during the elongation cycle of fatty acid biosynthesis. The fabG gene encodes the enzyme; in many bacteria a single copy is present, though some species harbor paralogs.

Biochemical properties and mechanism: FabG belongs to the short-chain dehydrogenase/reductase (SDR) superfamily. It typically features a Rossmann-like fold that binds NADPH and a catalytic Tyr-Lys dyad within a conserved active-site motif, often accompanied by the broader YXXXK motif. The cofactor-binding region may include a TGWXXGIG sequence. The enzyme generally functions as a homodimer and shows specificity for NADPH over NADH.

Role in fatty acid biosynthesis: The enzyme acts in the second step of the FAS II cycle, reducing the beta-ketoacyl-ACP substrate to beta-hydroxyacyl-ACP. The resulting hydroxyacyl-ACP then undergoes dehydration by FabA/FabZ and subsequent reduction by FabI to continue chain elongation, contributing to the production of saturated and unsaturated fatty acids incorporated into phospholipids.

Distribution and significance: FabG homologs are widespread among bacteria and are sometimes present as multiple paralogs. In contrast to human fatty acid synthesis, which uses a type I FAS system, the bacterial FAS II pathway—including FabG—is a potential target for antimicrobial intervention. While several FAS II enzymes have been explored for inhibition, FabG-specific inhibitors are not currently in clinical use.