N-acyl homoserine lactone synthase (AHL synthase) (AHL synthase)

N-acyl homoserine lactone (AHL) synthase is a bacterial enzyme, primarily found in Gram-negative Proteobacteria, that catalyzes the synthesis of AHL signaling molecules [11, 14]. These molecules serve as the primary autoinducers for quorum sensing, a sophisticated communication process that allows bacteria to coordinate gene expression in response to population density [1, 11]. The enzyme utilizes S-adenosyl-L-methionine (SAM) and acylated acyl carrier proteins (acyl-ACP) as substrates to produce AHLs, which then diffuse out of the cell to signal neighboring bacteria [9, 14]. At high concentrations, these signals bind to cognate LuxR-type receptors, triggering the expression of genes involved in biofilm formation, motility, and the production of various virulence factors [1, 17]. Because AHL synthase is essential for the pathogenicity of major human pathogens like Pseudomonas aeruginosa, it has become a prominent target for 'anti-virulence' or 'quorum-quenching' therapies [3, 17]. Inhibiting this enzyme aims to disrupt bacterial communication and 'disarm' the pathogen without imposing the strong selective pressure for resistance associated with traditional bactericidal antibiotics [1, 17]. Current research focuses on developing small-molecule inhibitors, including SAM analogs and substrate mimics, to treat chronic and multidrug-resistant infections [7, 9].

Other names

LuxI-type proteinAcyl-homoserine-lactone synthaseAutoinducer synthaseLuxI family proteinAcyl-HSL synthase

Inhibition of the synthesis of N-acyl homoserine lactone (AHL) signaling molecules by blocking the enzyme's active site or competing with its substrates, S-adenosyl-L-methionine (SAM) and acylated acyl carrier protein (acyl-ACP).