Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0018189 pyrroloquinoline quinone biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: This is the correct biological-process annotation for PqqA. UniProt identifies PqqA as required for PQQ biosynthesis and describes the peptide as the source of the cross-linked Glu-Tyr precursor used to form PQQ. The falcon deep-research synthesis confirms that PqqA is the ribosomally synthesized precursor peptide whose conserved Glu/Tyr residues become the PQQ scaffold, and that it is not a catalytic enzyme but the biosynthetic substrate of the pathway. The GO term definition itself states PQQ is synthesized from a small peptide containing tyrosine and glutamic acid that are cross-linked, matching PqqA exactly. Reason: PqqA is not a standalone enzyme, but it is a pathway precursor peptide required for pyrroloquinoline quinone biosynthesis; the BP annotation is the most appropriate representation of its core role. Supporting Evidence: file:PSEPK/pqqA/pqqA-uniprot.txt Required for coenzyme pyrroloquinoline quinone (PQQ) file:PSEPK/pqqA/pqqA-uniprot.txt Pyrroloquinoline quinone (Glu-Tyr) file:PSEPK/pqqA/pqqA-deep-research-falcon.md pqqA is explicitly identified as PP_0380 and as the peptide precursor for PQQ biosynthesis file:PSEPK/pqqA/pqqA-deep-research-falcon.md It is the substrate/precursor peptide from which PQQ is biosynthesized. The conserved glutamate (E) and tyrosine (Y) in the PqqA “core” provide the atoms that become cross-linked and transformed into the PQQ scaffold.

GO Term

Evidence

Action

Reason

GO:0018189 pyrroloquinoline quinone biosynthetic process

IEA
GO_REF:0000120

Summary: This is the correct biological-process annotation for PqqA. UniProt identifies PqqA as required for PQQ biosynthesis and describes the peptide as the source of the cross-linked Glu-Tyr precursor used to form PQQ. The falcon deep-research synthesis confirms that PqqA is the ribosomally synthesized precursor peptide whose conserved Glu/Tyr residues become the PQQ scaffold, and that it is not a catalytic enzyme but the biosynthetic substrate of the pathway. The GO term definition itself states PQQ is synthesized from a small peptide containing tyrosine and glutamic acid that are cross-linked, matching PqqA exactly.

Reason: PqqA is not a standalone enzyme, but it is a pathway precursor peptide required for pyrroloquinoline quinone biosynthesis; the BP annotation is the most appropriate representation of its core role.

Supporting Evidence:

file:PSEPK/pqqA/pqqA-uniprot.txt

Required for coenzyme pyrroloquinoline quinone (PQQ)

file:PSEPK/pqqA/pqqA-uniprot.txt

Pyrroloquinoline quinone (Glu-Tyr)

file:PSEPK/pqqA/pqqA-deep-research-falcon.md

pqqA is explicitly identified as PP_0380 and as the peptide precursor for PQQ biosynthesis

file:PSEPK/pqqA/pqqA-deep-research-falcon.md

It is the **substrate/precursor peptide** from which PQQ is biosynthesized. The conserved **glutamate (E)** and **tyrosine (Y)** in the PqqA “core” provide the atoms that become cross-linked and transformed into the PQQ scaffold.

Core Functions

PqqA is the ribosomally synthesized precursor peptide whose conserved glutamate (Glu15) and tyrosine (Tyr19) residues are cross-linked and excised to form the pyrroloquinoline quinone cofactor during PQQ biosynthesis; it functions as the biosynthetic substrate of the pathway rather than as an enzyme.

Directly Involved In:

pyrroloquinoline quinone biosynthetic process

Supporting Evidence:

file:PSEPK/pqqA/pqqA-uniprot.txt
Required for coenzyme pyrroloquinoline quinone (PQQ)
file:PSEPK/pqqA/pqqA-uniprot.txt
Pyrroloquinoline quinone (Glu-Tyr)
file:PSEPK/pqqA/pqqA-deep-research-falcon.md
PqqA is the **ribosomally synthesized precursor peptide** for pyrroloquinoline quinone (PQQ), a peptide-derived redox cofactor. The conserved **Glu** and **Tyr** residues in the PqqA core are the atoms ultimately transformed into the PQQ scaffold. PqqA is therefore **not a catalytic enzyme** but the biosynthetic substrate for the pathway.
file:PSEPK/pqqA/pqqA-deep-research-falcon.md
it is a short ribosomally synthesized precursor peptide that is post-translationally modified and processed to generate the small-molecule redox cofactor pyrroloquinoline quinone (PQQ)

Suggested Experiments

Experiment: Delete pqqA and complement with wild-type and Glu/Tyr substitution variants, then quantify cellular or secreted PQQ and activity of PQQ-dependent dehydrogenases.

Hypothesis: PqqA supplies the Glu-Tyr precursor required for PQQ production in KT2440.

Type: targeted genetics and metabolite analysis

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

NCBI PGAP External predictions

View prediction review YAML · pqqA-pgap-predictions-review.yaml · Review status: COMPLETE

NCBI PGAP names WP_003243383.1 "pyrroloquinoline quinone precursor peptide PqqA" from the TIGR02107 equivalog HMM and passes on two GO terms; no EC number is predicted. The name and the process term, pyrroloquinoline quinone biosynthetic process, are correct and match the main review. The function term, catalytic activity (GO:0003824), is wrong: PqqA is a 23-residue ribosomally made peptide whose conserved glutamate and tyrosine are cross-linked by the radical SAM enzyme PqqE and then excised to become PQQ. It is the pathway's substrate, not one of its enzymes. The model's own product name calls the protein a precursor peptide, so the error lies in the GO mapping of TIGR02107 itself and reaches every genome whose PqqA it names; the domain model NF019654 for the same family carries only the process term.

Source documents: genes/PSEPK/pqqA/pqqA-pgap-prediction-evidence/WP_003243383.1.gp · genes/PSEPK/pqqA/pqqA-pgap-prediction-evidence/pgap_models.yaml

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0003824 catalytic activity GO_MF

NPI — Nonparalog incorrect Review score: 0/2

Prediction method: NCBI PGAP · Version: GCF_000007565.2-RS_2026_02_04 (live); GO from WP_ record · PMID:33270901

CURATION MISTAKE

Review rationale: Wrong. PqqA is the precursor peptide of PQQ: PqqE (with the chaperone PqqD) cross-links its conserved Glu and Tyr side chains, and PqqF/G, PqqB and PqqC process the excised product. PqqA is acted upon and catalyses nothing, and the main review describes it as a pathway substrate rather than an enzyme. The root-level term carries no information and is false here. It comes from the TIGR02107 model's GO list, which contradicts the model's own product name ("precursor peptide"), so the mistake is on the HMM and propagates to every genome.

Supporting Evidence:

PMID:26961875: "The radical S -adenosylmethionine (SAM) protein PqqE is predicted to function in the pyrroloquinoline quinone (PQQ) biosynthetic pathway via catalysis of carbon-carbon bond formation between a glutamate and tyrosine side chain within the small peptide substrate PqqA."
PMID:30811189: "The first step is a C-C crosslinking reaction between the conserved Glu and Tyr residues within the peptide substrate PqqA"
file:PSEPK/pqqA/pqqA-pgap-prediction-evidence/pgap_models.yaml: "product_name: pyrroloquinoline quinone precursor peptide PqqA"

GO:0018189 pyrroloquinoline quinone biosynthetic process GO_BP

CNN — Correct but not novel Review score: 2/2

Prediction method: NCBI PGAP · Version: GCF_000007565.2-RS_2026_02_04 (live); GO from WP_ record · PMID:33270901

Review rationale: Correct and already in GOA (UniRule IEA), accepted by the main review as PqqA's core role. PqqA supplies the Glu and Tyr atoms that become PQQ, the scaffold case in which a substrate does part of the work of the process.

Supporting Evidence:

PMID:26961875: "The PQQ molecule derives from the evolutionarily conserved glutamate and tyrosine side chains within a ribosomally produced peptide substrate PqqA"
file:PSEPK/pqqA/pqqA-uniprot.txt: "FUNCTION: Required for coenzyme pyrroloquinoline quinone (PQQ)"

Deep Research

Falcon

(pqqA-deep-research-falcon.md)

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OpenScientist

(pqqA-deep-research-openscientist.md)

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📚 Additional Documentation

Notes

(pqqA-notes.md)

pqqA curation notes

2026-07-20 OpenScientist assessment

OpenScientist correctly identifies Q88QV4 as the 23-residue PQQ precursor
peptide and places Glu15 and Tyr19 at the conserved reactive positions.
The generated conservation artifact contains executable plotting code and
embedded sequences, but it omits source accessions for the claimed 25
reviewed orthologs. Its exact percentages and inferred leader boundary are
therefore not treated as verified evidence.
The curated precursor role and reactive residues remain supported by the
target UniProt sequence and established PqqA/PqqD/PqqE ortholog biochemistry.

pqqA

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

External Prediction Reviews

NCBI PGAP External predictions

Deep Research

Falcon

OpenScientist

📚 Additional Documentation

Notes

pqqA curation notes

2026-07-20 OpenScientist assessment

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