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.