aacs

UniProt ID: Q88IC8
Organism: Pseudomonas putida KT2440
Review Status: DRAFT
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Gene Description

Aacs is a predicted acetoacetate-CoA ligase that activates acetoacetate to acetoacetyl-CoA using ATP and coenzyme A. In KT2440 it is encoded near hbdH and bhbP, supporting a bacterial D-3-hydroxybutyrate utilization route that may use direct ATP-dependent acetoacetate activation; the physiological route and flux contribution of Q88IC8 have not been demonstrated directly.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0006629 lipid metabolic process
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: This broad InterPro-derived process overstates what is known for the KT2440 protein.
Reason: The mapping imports a broad lipid-process context from InterPro. The predicted ligase chemistry does not by itself establish that Q88IC8 participates in lipid metabolism in KT2440; evidence from mammalian AACS is not transferable to this bacterial candidate.
GO:0030729 acetoacetate-CoA ligase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: This is the defining EC- and family-supported Aacs reaction.
Reason: InterPro IPR005914 (Acac_CoA_synth), NCBIfam TIGR01217 (ac_ac_CoA_syn), CDD cd05943 (AACS) and PTHR42921:SF1 all place Q88IC8 in the acetoacetyl-CoA synthetase family of ANL-superfamily ligases. Family membership supports the ATP- and CoA-dependent activation of acetoacetate, a reaction demonstrated for the purified Zoogloea ramigera family member (PMID:7140777; evidence on that ortholog, not on Q88IC8). The submitter-supplied name and EC number are not used as support.
Supporting Evidence:
file:PSEPK/aacs/aacs-uniprot.txt
DR InterPro; IPR005914; Acac_CoA_synth.
file:PSEPK/aacs/aacs-uniprot.txt
DR NCBIfam; TIGR01217; ac_ac_CoA_syn; 1.

Core Functions

Predicted to activate acetoacetate to acetoacetyl-CoA using ATP and coenzyme A.

Molecular Function:
acetoacetate-CoA ligase activity
Supporting Evidence:
  • file:PSEPK/aacs/aacs-uniprot.txt
    Acetoacetyl-coenzyme A synthetase
  • PMID:7140777
    The enzyme absolutely required ATP, CoA, a monovalent cation (K+, Rb+, Cs+ or NH+4) and a divalent cation (Mg2+, Mn2+, Ca2+ or Ni2+) for the activation of acetoacetate, yielding acetoacetyl-CoA, AMP and pyrophosphate in equimolar amounts.

References

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Suggested Questions for Experts

Q: Is Aacs the principal acetoacetate-activation route during KT2440 growth on D-3-hydroxybutyrate?

Suggested Experiments

Experiment: Compare acetoacetate-CoA ligase activity, acetoacetyl-CoA abundance, and growth on D-3-hydroxybutyrate in wild type, aacs deletion, and complemented KT2440 strains.

Type: targeted metabolomics and carbon-source growth assay

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 · aacs-pgap-predictions-review.yaml · Review status: COMPLETE

NCBI PGAP names WP_010953970.1 "acetoacetate--CoA ligase" from the TIGR01217 equivalog HMM and passes on EC 6.2.1.16 with two GO terms. The name, the EC number and acetoacetate-CoA ligase activity are consistent with the InterPro, PANTHER and NCBIfam family assignments and with the main review. The process term, isopentenyl diphosphate biosynthesis via the mevalonate pathway (GO:0019287), is wrong for this organism. KT2440 makes isopentenyl diphosphate by the methylerythritol phosphate (DXP/MEP) route (Dxs, Dxr and IspD-H are present) and has no annotated HMG-CoA synthase, HMG-CoA reductase or mevalonate kinase, so acetoacetyl-CoA from Aacs cannot feed a mevalonate pathway. The mevalonate link reflects the mammalian cytosolic AACS, which supplies cholesterol synthesis; in bacteria the enzyme activates acetoacetate in poly-3-hydroxybutyrate and 3-hydroxybutyrate utilization. The error lies in the GO mapping of the TIGR01217 model itself, which imposes a lineage-specific pathway on every genome whose Aacs it names.

Source documents: genes/PSEPK/aacs/aacs-pgap-prediction-evidence/WP_010953970.1.gp · genes/PSEPK/aacs/aacs-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:0030729 acetoacetate-CoA ligase activity GO_MF
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 as a family-level prediction and already in GOA (IEA), where the main review accepts it. InterPro IPR005914, PANTHER PTHR42921:SF1 and NCBIfam TIGR01217/NF002937 all place Q88IC8 in the acetoacetyl-CoA synthetase family, whose bacterial members activate acetoacetate with ATP and CoA. Direct activity of the KT2440 protein has not been measured.
Supporting Evidence:
GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway GO_BP
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
PATHWAY CONTEXT IGNORED
Review rationale: Wrong for KT2440. The organism makes isopentenyl diphosphate by the DXP/MEP pathway: the reviewed Dxr and IspH entries for KT2440 are assigned to "isopentenyl diphosphate biosynthesis via DXP pathway". A UniProt search of KT2440 (taxon 160488, run 2026-10-19 while preparing this review) returned entries for the MEP enzymes (EC 2.2.1.7 Dxs, 1.1.1.267 Dxr, 4.6.1.12 IspF, 1.17.7.3 IspG) but none for the mevalonate-pathway enzymes HMG-CoA synthase (2.3.3.10), HMG-CoA reductase (1.1.1.34, 1.1.1.88), mevalonate kinase (2.7.1.36), phosphomevalonate kinase (2.7.4.2) or diphosphomevalonate decarboxylase (4.1.1.33). Bacterial acetoacetyl-CoA synthetases instead activate acetoacetate in the PHB cycle, consistent with the aacs neighbourhood (hbdH, bhbP) noted in the main review. The mevalonate term is a mammalian AACS context written onto the TIGR01217 model, so the error is on the HMM; it would be valid only in the minority of bacteria that do carry a mevalonate pathway.
Supporting Evidence:
  • file:PSEPK/dxr/dxr-uniprot.txt: "PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis"
  • file:PSEPK/ispH/ispH-uniprot.txt: "PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis"
  • PMID:10735852: "These findings suggest that acetoacetyl-CoA synthetase, rather than CoA transferase, activates acetoacetate to acetoacetyl-CoA in the S. meliloti poly-3-hydroxybutyrate cycle."
EC:6.2.1.16 EC 6.2.1.16 EC
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 not novel: EC 6.2.1.16 is already on the UniProt entry and underlies the GOA acetoacetate-CoA ligase annotation accepted in the main review. The family evidence is the same as for GO:0030729.
Supporting Evidence:

📚 Additional Documentation

Notes

(aacs-notes.md)

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