Acyl-Homoserine Lactone Biosynthesis: Structure and Mechanism

The first quorum-sensing system to be discovered was the Lux system of Vibrio fischeri, which regulates light production in the light organ of deep sea fish and squid via an acyl-homoserine lactone (AHL) signaling molecule. The LuxI-type AHL synthases catalyze the formation of the AHL from the substrates S-adenosyl-L-methionine (SAM) and acyl-acyl carrier protein (acyl-ACP). Enzymatic synthesis of AHLs using purified substrates for TraI (from Agrobacterium tumefaciens) verified that both SAM and acyl-ACP are substrates for AHL synthesis in vitro. X-ray crystallographic structural analyses of two LuxI-type AHL synthases form the basis of the current molecular understanding of AHL synthesis. The structure of the EsaI enzyme from Pantoea stewartii was determined from the native sequence. The structure of the LasI enzyme from Pseudomonas aeruginosa was determined from an active form that had been engineered to improve solubility and crystallization properties. The LasI structure provided a less clear explanation for the selectivity of AHL synthases for acyl-ACPs with long acyl chains. The LasI acyl-chain binding pocket is actually an elongated tunnel through the enzyme that is formed by hydrophobic residues at similar positions in the enzyme as those in the EsaI pocket. The residues in EsaI that occlude the pocket are larger than those in the same position in LasI, which limits the acyl chain size to a C6 acyl-chain.