Enoyl-acyl carrier protein reductase FabK (FabK)

Enoyl-acyl carrier protein reductase FabK is a flavoprotein enzyme found in certain bacterial fatty acid synthesis pathways (type II FAS). Unlike other enoyl-ACP reductases (FabI, FabL, FabV), FabK features a TIM barrel structure and utilizes flavin mononucleotide (FMN) as a cofactor, with NADH serving as a reductant. FabK catalyzes the reduction of enoyl-ACP substrates during fatty acid elongation via a ping-pong bi-bi mechanism that involves indirect hydride transfer from NADH to the substrate through FMN. Its activity is sensitive to monovalent cation salts and displays some NADH oxidase activity, even without substrate. FabK is present in pathogens such as Streptococcus pneumoniae, Enterococcus faecalis, Listeria monocytogenes, and Porphyromonas gingivalis, where it contributes to cell membrane synthesis and survival. Due to FabK's essential role in bacterial physiology and its structural divergence from human enzymes, it represents a promising target for the development of new antibacterial agents, especially given growing resistance to existing fatty acid synthesis inhibitors.

Other names

FabKEnoyl-ACP reductase II (sometimes specified as type II)Enoyl-acyl carrier protein reductase KFlavin-dependent enoyl-ACP reductase

Competitive or noncompetitive inhibition of FMN cofactor or substrate binding site, leading to blocked fatty acid biosynthesis and bacterial cell death