pqsC (Q9I4X1, PA0998) — review notes

Part of the BGC exemplar curation project (projects/BGC.md). MIBiG BGC0000922
(P. aeruginosa PAO1, 2-alkyl-4-quinolone / PQS-precursor cluster). GenBank
AAG04387.1 → UniProt Q9I4X1 (PQSC_PSEAE), gene pqsC / PA0998.

Function

PqsC is the catalytic subunit of the heterodimeric condensing enzyme PqsBC,
which catalyzes the second step of 2-alkyl-4(1H)-quinolone (AQ / HAQ) biosynthesis
in the pqs quorum-sensing pathway.

Pathway (two steps): PqsD makes 2-aminobenzoylacetate (2-ABA) from
anthraniloyl-CoA + malonyl-CoA; then PqsBC catalyzes the decarboxylative
coupling of 2-ABA to an octanoyl group carried on PqsC to give
2-heptyl-4(1H)-quinolone (HHQ), the direct precursor of PQS
(2-heptyl-3-hydroxy-4(1H)-quinolone; PqsH then adds the 3-OH).
PMID:24239007
EC 2.3.1.230 "2-heptyl-4(1H)-quinolone synthase": reaction
(2-aminobenzoyl)acetate + octanoyl-CoA + H+ = 2-heptyl-4(1H)-quinolone + CO2 + CoA
(UniProt Q9I4X1; ECO:0000269|PMID:24239007, ECO:0000269|PMID:26811339).
Crystal structure (PDB 5DWZ): PqsBC is an obligate heterodimer; PqsC
carries the catalytic active site Cys-129 / His-269; PqsB lacks these
catalytic residues and is the non-catalytic partner.
PMID:26811339

Annotation issues identified

GO:0006633 fatty acid biosynthetic process (IEA) — over-propagation from the
β-ketoacyl-ACP synthase III (FabH/KAS III) InterPro signature. PqsBC is NOT a
fatty-acid synthase: octanoate is a substrate, and the product is a quinolone
QS signal, not a fatty acid. The Dulcey 2013 paper is explicitly titled to make
this point ("...derive from fatty acids, not 3-ketofatty acids"). → REMOVE.
GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity (IEA) — same
KAS-III-fold over-annotation; the enzyme does not perform the FabH ACP-dependent
Claisen condensation of fatty-acid synthesis. → MODIFY to the accurate parent
GO:0016747; propose specific new term for EC 2.3.1.230.
No GO MF term exists for EC 2.3.1.230 → proposed_new_terms:
"2-heptyl-4(1H)-quinolone synthase activity".

Predicted-complex evidence (BGC project)

Moriwaki et al. (bioRxiv 2025.10.26.684697) predict the PqsB–PqsC heterodimer
(BGC0000922; AAG04386.1/AAG04387.1) at ipTM 0.95, structurally matching PDB
5DWZ — consistent with the experimentally established obligate heterodimer.

References

PMID:24239007 — Dulcey et al. 2013, Chem Biol (pathway/mechanism). VERIFIED.
PMID:26811339 — Drees et al. 2016, JBC (PqsBC crystal structure, 5DWZ). VERIFIED.
PMID:12426334 — Gallagher et al. 2002, J Bacteriol (pqs genetics; IMP source). VERIFIED.

PseudoCAP IBA-seed assessment

Audit added 2026-10-28 (PseudoCAP IBA-seed project, worklist rank 36). The
review itself was not rewritten.

PTN node	node term	n_seeds	leaf IBAs	seed annotation (term, evidence, PMID)	verdict	rationale
PTN002147059 (PTHR34069)	GO:0044550 secondary metabolite biosynthetic process	1 (sole seed)	30 (17 taxa)	GO:0044550, IMP, PMID:12426334 (PseudoCAP)	SOUND (seed); node placed too high	The seed is direct for PqsC: the screen's own pqsC (PA0998) transposon mutant lost PQS PMID:12426334, and later biochemistry shows that PqsBC makes HHQ (PMID:24239007, PMID:26811339). The PAINT leaf file, however, shows that the node sits above canonical FabH (KAS III) enzymes of primary fatty acid synthesis: H. influenzae FabH P43711, B. subtilis FabHB O07600, P. aeruginosa FabH Q9HYR2 and PA3286 Q9HYV7, Plasmodium FabH Q7KWI9, Chlamydia FabH O84242, Xanthomonas FabH Q8P810 and others. For those leaves the term is wrong. The PseudoCAP row needs no defect. I recorded a GO_CENTRAL `WRONG_TERM`/CHECK defect on the pqsC IBA row, asking for the IBD to move down to a PqsC-only node.

Row consistency: the IBA and IMP rows for GO:0044550 stay ACCEPT because the
claim is true for PqsC. I added a direct quote from the Discussion of
PMID:12426334 to both rows. The cached PTHR34069 family review calls this node
SOUND only because PqsC is its one reviewed recipient. The leaf list above
contradicts that, but the file is outside this audit's scope.