Beta-ketoacyl-(acyl carrier protein) synthase III (PqsBC) (PqsBC)

PqsBC is a heterodimeric enzyme complex in the opportunistic pathogen Pseudomonas aeruginosa, composed of the PqsB and PqsC subunits [1, 3]. It belongs to the beta-ketoacyl-acyl carrier protein synthase III (FabH) family and is specifically responsible for the condensation of 2-aminobenzoylacetate (2-ABA) with octanoyl-CoA to produce 2-heptyl-4-quinolone (HHQ) [1, 2]. HHQ serves as the immediate precursor to the Pseudomonas quinolone signal (PQS), a critical autoinducer in one of the primary quorum-sensing systems used by the bacterium to regulate virulence factors such as pyocyanin, elastase, and biofilm formation [2, 5]. Due to its central role in the alkylquinolone biosynthetic pathway, PqsBC has emerged as a prominent target for anti-virulence drug development aimed at disrupting bacterial communication rather than killing the pathogen [3, 4]. Inhibiting PqsBC effectively attenuates the pathogen's ability to coordinate damage and evade the host immune system, which is of significant interest for treating chronic lung infections in cystic fibrosis patients [4, 5]. Experimental inhibitors, including the natural competitive inhibitor 2-aminoacetophenone and various synthetic benzamide-benzimidazole derivatives, have demonstrated the potential to block HHQ production and reduce virulence factor expression [1, 4].

Other names

PqsB/PqsC complex2-heptyl-4-quinolone synthaseAlkylquinolone biosynthesis enzymePqsB/C heterodimerHHQ synthase

Inhibits the condensation of 2-aminobenzoylacetate and octanoyl-CoA, thereby blocking the synthesis of the quorum-sensing signal 2-heptyl-4-quinolone (HHQ).