UDP-N-acetylglucosamine acyltransferase (LpxA)

UDP-N-acetylglucosamine acyltransferase (LpxA) is a critical enzyme that catalyzes the first step of the Raetz pathway, the biosynthetic route for lipid A in Gram-negative bacteria (UniProt P0A722). Lipid A serves as the hydrophobic anchor for lipopolysaccharide (LPS), which is an essential component of the bacterial outer membrane and a potent endotoxin (PubMed: 19046621). LpxA transfers an acyl group from R-3-hydroxyacyl-acyl carrier protein to the 3-OH position of UDP-N-acetylglucosamine (PubChem CID: 119035). Because this enzyme is essential for the viability of most Gram-negative pathogens and has no mammalian homolog, it is considered a highly attractive target for the development of novel antibiotics (PubMed: 26153773). Inhibition of LpxA leads to the depletion of LPS, compromising the integrity of the bacterial cell envelope and resulting in growth arrest or cell death (PubMed: 22403570).

Other names

UDP-GlcNAc acyltransferaseAcyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferaseLpxAUDP-N-acetylglucosamine 3-O-acyltransferase

Inhibition of the first committed step of the Raetz pathway for lipid A biosynthesis, preventing the formation of the Gram-negative outer membrane and leading to bacterial cell death.