id: Q88IC8 gene_symbol: aacs taxon: id: NCBITaxon:160488 label: Pseudomonas putida KT2440 status: COMPLETE locus_tag: PP_3071 description: >- 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. references: - id: PMID:33270901 title: 'RefSeq: expanding the Prokaryotic Genome Annotation Pipeline reach with protein family model curation.' - id: PMID:7140777 title: Purification and characterization of acetoacetyl-CoA synthetase from Zoogloea ramigera I-16-M. - id: PMID:10735852 title: Requirement for the enzymes acetoacetyl coenzyme A synthetase and poly-3-hydroxybutyrate (PHB) synthase for growth of Sinorhizobium meliloti on PHB cycle intermediates. - id: file:PSEPK/aacs/aacs-uniprot.txt title: UniProtKB entry for aacs (Q88IC8) - id: file:PSEPK/dxr/dxr-uniprot.txt title: UniProtKB entry for dxr (Q88MH4) - id: file:PSEPK/ispH/ispH-uniprot.txt title: UniProtKB entry for ispH (Q88Q89) - id: file:PSEPK/aacs/aacs-pgap-prediction-evidence/WP_010953970.1.gp title: RefSeq GenPept record WP_010953970.1 - id: file:PSEPK/aacs/aacs-pgap-prediction-evidence/pgap_models.yaml title: PGAP naming model and matched NCBI HMMs for aacs source_documents: - genes/PSEPK/aacs/aacs-pgap-prediction-evidence/WP_010953970.1.gp - genes/PSEPK/aacs/aacs-pgap-prediction-evidence/pgap_models.yaml predictions: - source_method: NCBI PGAP source_version: GCF_000007565.2-RS_2026_02_04 (live); GO from WP_ record source_reference_id: PMID:33270901 predicted_term: id: GO:0030729 label: acetoacetate-CoA ligase activity predicted_term_type: GO_MF review: assessment: CNN confidence_score: 2 summary: >- 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. supported_by: - reference_id: file:PSEPK/aacs/aacs-uniprot.txt supporting_text: "DR InterPro; IPR005914; Acac_CoA_synth." - reference_id: file:PSEPK/aacs/aacs-uniprot.txt supporting_text: "DR PANTHER; PTHR42921:SF1; ACETOACETYL-COA SYNTHETASE; 1." - reference_id: PMID:7140777 supporting_text: "for the activation of acetoacetate, yielding acetoacetyl-CoA, AMP and pyrophosphate in equimolar amounts." - source_method: NCBI PGAP source_version: GCF_000007565.2-RS_2026_02_04 (live); GO from WP_ record source_reference_id: PMID:33270901 predicted_term: id: GO:0019287 label: isopentenyl diphosphate biosynthetic process, mevalonate pathway predicted_term_type: GO_BP review: assessment: NPI confidence_score: 0 error_type: PATHWAY_CONTEXT_IGNORED summary: >- 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. supported_by: - reference_id: file:PSEPK/dxr/dxr-uniprot.txt supporting_text: "PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis" - reference_id: file:PSEPK/ispH/ispH-uniprot.txt supporting_text: "PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis" - reference_id: PMID:10735852 supporting_text: "These findings suggest that acetoacetyl-CoA synthetase, rather than CoA transferase, activates acetoacetate to acetoacetyl-CoA in the S. meliloti poly-3-hydroxybutyrate cycle." - source_method: NCBI PGAP source_version: GCF_000007565.2-RS_2026_02_04 (live); GO from WP_ record source_reference_id: PMID:33270901 predicted_term: id: EC:6.2.1.16 label: EC 6.2.1.16 predicted_term_type: EC review: assessment: CNN confidence_score: 2 summary: >- 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. supported_by: - reference_id: file:PSEPK/aacs/aacs-uniprot.txt supporting_text: "DR NCBIfam; TIGR01217; ac_ac_CoA_syn; 1."