PqsC (PA0998) is the catalytic subunit of the heterodimeric condensing enzyme PqsBC, which carries out the second step of 2-alkyl-4(1H)-quinolone (AQ/HAQ) biosynthesis in the Pseudomonas aeruginosa pqs quorum-sensing pathway. After PqsD generates 2-aminobenzoylacetate (2-ABA) from anthraniloyl-CoA and malonyl-CoA, PqsBC catalyzes the decarboxylative coupling of 2-ABA with an octanoyl group (from octanoyl-CoA) carried on PqsC to produce 2-heptyl-4(1H)-quinolone (HHQ), the direct precursor of the Pseudomonas quinolone signal PQS (PMID:24239007). PqsC adopts a beta-ketoacyl-ACP synthase III (FabH/KAS III) fold but does not catalyze a fatty-acid synthase reaction; its reaction is EC 2.3.1.230 ("2-heptyl-4(1H)-quinolone synthase"), with an active site formed by Cys-129 and His-269 (PMID:26811339). The enzyme is an obligate heterodimer: PqsB is catalytically inactive but tightly associated and required for activity. The AQ signals it helps produce control biofilm development and numerous virulence factors, making PqsBC a target for anti-virulence drug development.
Definition: Catalysis of the reaction: (2-aminobenzoyl)acetate + octanoyl-CoA + H+ = 2-heptyl-4(1H)-quinolone + CO2 + CoA. This decarboxylative condensation, carried out by the PqsBC heterodimer (catalytic subunit PqsC), is the penultimate step in Pseudomonas quinolone signal (PQS) biosynthesis.
Justification: EC 2.3.1.230 ("2-heptyl-4(1H)-quinolone synthase") has no corresponding GO molecular function term. The existing IEA annotation GO:0004315 (3-oxoacyl-[acyl-carrier-protein] synthase activity) is a fold-based misassignment, and GO:0016747 (its proposed replacement) is only a general parent. A specific term would accurately capture the activity of PqsC/PqsBC.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0044550 secondary metabolite biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) inference that PqsC participates in secondary metabolite biosynthesis. PqsC is the catalytic subunit of the PqsBC condensing enzyme that makes the alkylquinolone (HAQ) secondary metabolites, so this is correct. Reason: Core biological process. HAQs/HHQ are secondary metabolites (quorum-sensing signals); PqsC is essential for their biosynthesis. Consistent with the experimental IMP annotation (PMID:12426334) below. Supporting Evidence: PMID:24239007 HAQ biosynthesis, which requires the PqsABCD enzymes, proceeds by a two-step pathway |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based (IEA) assignment from the beta-ketoacyl-ACP synthase III (FabH/KAS III) signature. PqsC adopts this fold but does NOT catalyze the ACP-dependent Claisen condensation of fatty-acid synthesis; it catalyzes the decarboxylative coupling of 2-ABA with octanoyl-CoA to form HHQ (EC 2.3.1.230). The term is therefore wrong-specific. Reason: The fold-based prediction picks the wrong specific activity. The accurate activity is an acyl transfer (not a 3-oxoacyl-ACP/fatty-acid synthase reaction). Replace with the accurate parent GO:0016747 and propose a specific new term for EC 2.3.1.230 (see proposed_new_terms). Proposed replacements: acyltransferase activity, transferring groups other than amino-acyl groups Supporting Evidence: PMID:26811339 does not form a catalytic triad with His-269 and Cys-129, and in its place a valine (Val-299) is present PMID:24239007 the decarboxylating coupling of 2-ABA to an octanoate group linked to PqsC produces HHQ |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Subcellular-location IEA. Consistent with the experimental cytoplasmic localization (EXP, PMID:24239007) below and with PqsBC being a soluble cytoplasmic condensing enzyme. Reason: Correct cellular component; corroborated by experimental evidence. |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000002 | REMOVE | Summary: InterPro-based (IEA) over-propagation from the KAS III (FabH) signature. PqsBC is not part of fatty-acid biosynthesis: an octanoyl group is a SUBSTRATE, and the PRODUCT is a quinolone quorum-sensing signal, not a fatty acid. Dulcey et al. (2013) explicitly established that HAQs derive from fatty acids rather than being made by a fatty-acid-synthase-type pathway. Reason: Demonstrably incorrect biological process. The enzyme consumes a fatty acyl substrate but synthesizes an alkylquinolone; assigning fatty acid biosynthesis is a domain-propagation error. Supporting Evidence: PMID:24239007 the pseudomonas signaling molecules 4-hydroxy-2-alkylquinolines derive from fatty acids, not 3-ketofatty acids |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based (IEA) general acyltransferase activity. This broad parent is accurate for PqsC: the EC 2.3.1.230 reaction transfers an octanoyl/acyl group in a decarboxylative condensation. It is correct but uninformative relative to the specific activity proposed in proposed_new_terms. Reason: Correct general molecular function (true parent of the specific HHQ-synthase activity). Retained as an accurate, if non-specific, MF. Supporting Evidence: PMID:24239007 the decarboxylating coupling of 2-ABA to an octanoate group linked to PqsC produces HHQ |
| GO:0005737 cytoplasm | EXP PMID:24239007 The end of an old hypothesis: the pseudomonas signaling mole... | ACCEPT | Summary: Experimental cytoplasmic localization, consistent with PqsBC functioning as a soluble cytoplasmic condensing enzyme. Reason: Experimentally supported cellular component. |
| GO:0044550 secondary metabolite biosynthetic process | IMP PMID:12426334 Functions required for extracellular quinolone signaling by ... | ACCEPT | Summary: Experimental (IMP) evidence that pqs genes are required for extracellular quinolone signal synthesis. PqsC is essential for HHQ/HAQ production. Reason: Core biological process with direct experimental (mutant phenotype) support. This is the defining process for the gene. Supporting Evidence: PMID:12426334 Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa |
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Download this section (compressed HTML)Q: Per GO guidelines the 2-heptyl-4(1H)-quinolone synthase activity (EC 2.3.1.230) is annotated to the catalytic subunit PqsC (enables); should the required but non-catalytic PqsB additionally carry a contributes_to to reflect that the activity is realized only in the assembled PqsBC heterodimer?
Experiment: Targeted active-site mutagenesis (Cys-129, His-269) coupled to in vitro HHQ synthase assays to formally delimit which steps require each residue, confirming the GO term boundary for the proposed 2-heptyl-4(1H)-quinolone synthase activity.
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