identifier: METPO:1000846
label: Homoacetogenesis
definition: A metabolism in which acetate is produced as the sole reduced end product
  from reduction of CO2 via the acetyl-CoA pathway.
definition_source: DOI:10.1016/j.tibtech.2019.05.008
trait_category: METABOLISM
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- METPO:1000060
synonyms:
- synonym_text: Reductive acetyl-CoA pathway
  synonym_type: RELATED_SYNONYM
  source: metpo.owl
- synonym_text: Wood-Ljungdahl pathway
  synonym_type: RELATED_SYNONYM
  source: metpo.owl
evidence:
- reference: DOI:10.1016/j.tibtech.2019.05.008
  snippet: two mol of carbon dioxide are reduced to one mol of acetyl-CoA
  notes: Review supports Wood-Ljungdahl reduction of CO2 to acetyl-CoA and acetate.
- reference: DOI:10.1016/j.bbapap.2008.08.012
  snippet: Wood-Ljungdahl Pathway of CO2 Fixation
  notes: Review supports acetogens using the Wood-Ljungdahl pathway for CO2 fixation.
canonical_examples:
- taxon_id: NCBITaxon:33952
  taxon_label: Acetobacterium woodii
  note: "Model homoacetogen; reduces CO2 to acetate via the Wood-Ljungdahl pathway (Rnf bioenergetics model)."
  reference: PMID:22479398
causal_graphs:
- graph_id: homoacetogenesis_wood_ljungdahl_acetate
  title: Homoacetogenesis Wood-Ljungdahl acetate mechanism
  description: DOI-backed graph linking anaerobic CO2 reduction, hydrogen/CO inputs,
    acetyl-CoA synthesis, and acetate as the sole reduced product.
  nodes:
  - node_id: homoacetogenesis_trait
    label: Homoacetogenesis
    node_type: TRAIT
    grounding: METPO:1000846
    description: Acetate-producing metabolism through the reductive acetyl-CoA pathway.
  - node_id: anaerobic_condition
    label: anaerobic condition
    node_type: ENVIRONMENTAL_FACTOR
    description: Oxygen-free condition associated with acetogens.
    grounding: PATO:0001456
  - node_id: wood_ljungdahl_pathway
    label: Wood-Ljungdahl pathway
    node_type: PATHWAY
    description: Reductive acetyl-CoA pathway used for CO2 fixation.
    grounding: GO:0030634
  - node_id: carbon_dioxide
    label: carbon dioxide
    node_type: CHEMICAL
    grounding: CHEBI:16526
    description: C1 carbon input reduced during homoacetogenesis.
  - node_id: molecular_hydrogen
    label: molecular hydrogen
    node_type: CHEMICAL
    grounding: CHEBI:18276
    description: Electron donor for CO2 reduction in many homoacetogens.
  - node_id: carbon_monoxide
    label: carbon monoxide
    node_type: CHEMICAL
    grounding: CHEBI:17245
    description: C1 substrate or intermediate in acetyl-CoA synthesis.
  - node_id: acetyl_coa
    label: acetyl-CoA
    node_type: CHEMICAL
    grounding: CHEBI:15351
    description: Central product of Wood-Ljungdahl carbon fixation.
  - node_id: acetate
    label: acetate
    node_type: CHEMICAL
    grounding: CHEBI:30089
    description: Sole reduced end product in homoacetogenesis.
  - node_id: atp
    label: ATP
    node_type: CHEMICAL
    grounding: CHEBI:30616
    description: Energy carrier conserved during acetate formation.
  - node_id: formate
    label: formate
    node_type: CHEMICAL
    description: C1 intermediate in the methyl branch of the Wood-Ljungdahl pathway.
  - node_id: formate_dehydrogenase
    label: formate dehydrogenase
    node_type: GENE_OR_PROTEIN
    description: Enzyme reducing CO2 to formate in the methyl branch.
    grounding: UniProtKB:A0A016XII7
  - node_id: formyl_thf
    label: formyl-tetrahydrofolate
    node_type: CHEMICAL
    description: Formyl-THF, the C1-loaded folate intermediate of the methyl branch.
  - node_id: formyl_thf_synthetase
    label: formyl-THF synthetase (Fhs)
    node_type: GENE_OR_PROTEIN
    description: Formate--tetrahydrofolate ligase converting formate to formyl-THF.
  - node_id: methyl_branch
    label: methyl branch of WLP
    node_type: PATHWAY
    description: Eastern/methyl branch generating the methyl group of acetyl-CoA.
  - node_id: carbonyl_branch
    label: carbonyl branch of WLP
    node_type: PATHWAY
    description: Western/carbonyl branch generating the carbonyl group via CO.
  - node_id: acs_codh_complex
    label: ACS/CODH complex
    node_type: GENE_OR_PROTEIN
    description: Acetyl-CoA synthase / CO dehydrogenase complex where the two WLP
      branches converge.
  - node_id: acetate_kinase
    label: acetate kinase
    node_type: GENE_OR_PROTEIN
    description: Enzyme generating ATP by substrate-level phosphorylation during acetate
      formation.
    grounding: UniProtKB:A0A081KVG3
  - node_id: substrate_level_phosphorylation
    label: substrate-level phosphorylation
    node_type: BIOLOGICAL_PROCESS
    description: ATP-generating phosphoryl transfer at acetate kinase in the WLP.
  - node_id: energy_conservation_module
    label: membrane energy-conservation module (Rnf/Ech)
    node_type: GENE_OR_PROTEIN
    description: Membrane-associated Rnf or Ech complex translocating ions to build
      the transmembrane gradient.
  - node_id: transmembrane_ion_gradient
    label: transmembrane ion gradient
    node_type: BIOLOGICAL_PROCESS
    description: Na+/H+ electrochemical gradient driving ATP synthase during acetogenesis.
  - node_id: atp_synthase
    label: ATP synthase
    node_type: GENE_OR_PROTEIN
    description: Membrane enzyme using the ion gradient to synthesize ATP.
    grounding: UniProtKB:A0A415TT77
  edges:
  - subject: homoacetogenesis_trait
    predicate: occurs in
    object: anaerobic_condition
    description: Homoacetogenesis is an anaerobic acetogenic metabolism.
    evidence:
    - reference: DOI:10.1023/A:1020514617738
      snippet: obligately anaerobic bacteria
      notes: Supports anaerobic context for acetogens.
    predicate_id: biolink:occurs_in
  - subject: homoacetogenesis_trait
    predicate: has mechanistic pathway
    object: wood_ljungdahl_pathway
    description: Homoacetogenesis proceeds through the Wood-Ljungdahl pathway.
    evidence:
    - reference: DOI:10.1016/j.tibtech.2019.05.008
      snippet: Wood-Ljungdahl pathway
      notes: Supports pathway assignment for acetogens.
  - subject: carbon_dioxide
    predicate: participates in
    object: wood_ljungdahl_pathway
    description: CO2 is reduced through the Wood-Ljungdahl pathway.
    evidence:
    - reference: DOI:10.1016/j.tibtech.2019.05.008
      snippet: carbon dioxide are reduced
      notes: Supports CO2 as substrate.
    predicate_id: biolink:participates_in
  - subject: molecular_hydrogen
    predicate: provides electrons for
    object: wood_ljungdahl_pathway
    description: Hydrogen can provide reducing equivalents for CO2 reduction.
    evidence:
    - reference: DOI:10.1016/j.bbapap.2008.08.012
      snippet: acetyl-CoA from CO or CO2 + H2
      notes: Supports H2 as an electron donor with CO2.
    predicate_id: METPO:2007402
  - subject: carbon_monoxide
    predicate: participates in
    object: wood_ljungdahl_pathway
    description: CO can serve as a C1 input or intermediate for acetyl-CoA synthesis.
    evidence:
    - reference: DOI:10.1016/j.bbapap.2008.08.012
      snippet: acetyl-CoA from CO or CO2 + H2
      notes: Supports CO as substrate or intermediate.
    predicate_id: biolink:participates_in
  - subject: wood_ljungdahl_pathway
    predicate: produces
    object: acetyl_coa
    description: Wood-Ljungdahl carbon fixation produces acetyl-CoA.
    evidence:
    - reference: DOI:10.1016/j.tibtech.2019.05.008
      snippet: reduced to one mol of acetyl-CoA
      notes: Supports acetyl-CoA synthesis from CO2.
    predicate_id: METPO:2000202
  - subject: acetyl_coa
    predicate: converted to
    object: acetate
    description: Acetyl-CoA is converted to acetate as the reduced product.
    evidence:
    - reference: DOI:10.1016/j.tibtech.2019.05.008
      snippet: further to acetate
      notes: Supports acetate formation downstream of acetyl-CoA.
  - subject: homoacetogenesis_trait
    predicate: produces
    object: acetate
    description: Homoacetogenesis produces acetate as the sole reduced end product.
    evidence:
    - reference: DOI:10.1023/A:1020514617738
      snippet: reduce CO2 to acetate
      notes: Supports acetate as the defining acetogenic product.
    predicate_id: METPO:2000202
  - subject: acetyl_coa
    predicate: supports formation of
    object: atp
    description: Conversion to acetate can conserve energy as ATP.
    evidence:
    - reference: DOI:10.1016/j.tibtech.2019.05.008
      snippet: further to acetate
      notes: Review discusses acetate formation as the energy-conserving product branch.
  - subject: carbon_dioxide
    predicate: reduced by enzyme to
    object: formate
    description: CO2 is reduced to formate by formate dehydrogenase in the methyl
      branch.
    evidence:
    - reference: DOI:10.1039/d4cb00099d
      notes: CO2 to formate catalyzed by formate dehydrogenase (Fdh); core WLP methyl-branch
        step.
  - subject: formate_dehydrogenase
    predicate: catalyzes
    object: formate
    description: Formate dehydrogenase produces formate from CO2.
    evidence:
    - reference: DOI:10.1039/d4cb00099d
      notes: CO2 -> formate catalyzed by formate dehydrogenase (Fdh).
    predicate_id: biolink:catalyzes
  - subject: formate
    predicate: converted by enzyme to
    object: formyl_thf
    description: Formate is converted to formyl-THF by formyl-THF synthetase.
    evidence:
    - reference: DOI:10.1039/d4cb00099d
      notes: formate -> formyl-THF by formyl-THF synthetase (Fhs); methyl-branch step.
  - subject: formyl_thf_synthetase
    predicate: catalyzes
    object: formyl_thf
    description: Formyl-THF synthetase (Fhs) forms formyl-THF from formate.
    evidence:
    - reference: DOI:10.1039/d4cb00099d
      notes: formate -> formyl-THF by formyl-THF synthetase (Fhs).
    predicate_id: biolink:catalyzes
  - subject: methyl_branch
    predicate: converges with
    object: carbonyl_branch
    description: The methyl and carbonyl branches of the WLP converge at the ACS/CODH
      complex.
    evidence:
    - reference: DOI:10.1186/s13068-024-02554-w
      notes: eastern/methyl branch and carbonyl/western branch meet at the acetyl-CoA
        synthase/carbon monoxide dehydrogenase complex (ACS/CODH); canonical WLP architecture.
  - subject: acs_codh_complex
    predicate: produces
    object: acetyl_coa
    description: The ACS/CODH complex condenses the methyl and carbonyl groups into
      acetyl-CoA.
    evidence:
    - reference: DOI:10.1186/s13068-024-02554-w
      notes: the two WLP branches meet at the ACS/CODH complex to form acetyl-CoA.
    predicate_id: METPO:2000202
  - subject: acetate_kinase
    predicate: generates
    object: atp
    description: Acetate kinase generates ATP by substrate-level phosphorylation during
      acetate formation, the only WLP ATP-yielding step.
    evidence:
    - reference: DOI:10.1039/d4cb00099d
      notes: acetyl-CoA -> acetate via acetyl-phosphate with ATP from substrate-level
        phosphorylation (acetate kinase); WLP is otherwise net-zero ATP.
    predicate_id: biolink:produces
  - subject: acetate_kinase
    predicate: participates in
    object: substrate_level_phosphorylation
    description: Acetate kinase mediates substrate-level phosphorylation in the acetate
      branch.
    evidence:
    - reference: DOI:10.1039/d4cb00099d
      notes: ATP from substrate-level phosphorylation at acetate kinase.
    predicate_id: biolink:participates_in
  - subject: energy_conservation_module
    predicate: generates
    object: transmembrane_ion_gradient
    description: The membrane Rnf or Ech module translocates Na+/H+ to generate the
      transmembrane ion gradient.
    evidence:
    - reference: DOI:10.1039/d4cb00099d
      notes: Rnf transfers electrons from Fdred to NAD+ while translocating Na+/H+;
        Ech acts as Fd:H+ oxidoreductase.
    - reference: DOI:10.3389/fmicb.2023.1185739
      notes: membrane-associated energy-conservation module involving Rnf or Ech plus
        ATP synthase.
    predicate_id: biolink:produces
  - subject: transmembrane_ion_gradient
    predicate: drives
    object: atp_synthase
    description: The transmembrane ion gradient drives ATP synthase to conserve energy
      during acetogenesis.
    evidence:
    - reference: DOI:10.3389/fmicb.2023.1185739
      notes: membrane-associated energy-conservation module ... plus ATP synthase.
  - subject: atp_synthase
    predicate: produces
    object: atp
    description: ATP synthase produces ATP from the ion gradient, conserving energy
      in the near-thermodynamic-limit acetogenic metabolism.
    evidence:
    - reference: DOI:10.3389/fmicb.2023.1185739
      notes: ATP synthase couples the ion gradient to ATP synthesis in acetogens.
    predicate_id: METPO:2000202
curation_history:
- timestamp: '2026-05-05T01:35:46.916045+00:00'
  curator: seed_from_metpo
  action: SEEDED_FROM_METPO
  changes: imported from data/raw/metpo.owl (CLASS)
  llm_assisted: false
- timestamp: '2026-05-08T00:00:00-07:00'
  curator: codex
  action: ADDED_CAUSAL_GRAPH
  changes: Added DOI-backed causal graph for anaerobic Wood-Ljungdahl CO2 reduction,
    H2/CO inputs, acetyl-CoA formation, acetate product formation, and ATP conservation.
  llm_assisted: true
- timestamp: '2026-05-20T03:35:30Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2000202×2).
  llm_assisted: true
- timestamp: '2026-05-24T04:38:00Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv
    (ENVO:01001057×1, GO:0046358×1).
  llm_assisted: true
- timestamp: '2026-05-26T05:00:47Z'
  curator: claude
  action: RENAME_PREDICATE_LABELS
  changes: 'Renamed 3 causal-edge predicate label(s) to align with existing groundings:
    input to → participates in ×2; occurs under → occurs in ×1.'
  llm_assisted: true
- timestamp: '2026-05-26T05:00:50Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (biolink:participates_in×2, biolink:occurs_in×1).
  llm_assisted: true
- timestamp: '2026-06-14T07:26:19Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2007402×1).
  llm_assisted: true
- timestamp: '2026-06-15T07:19:08Z'
  curator: claude
  action: FIX_NODE_GROUNDING_CURIE
  changes: Overwrote 1 causal-node grounding(s) to corrected CURIEs (phase-2 id-label
    fix; verified vs OAK).
  llm_assisted: true
- timestamp: '2026-06-15T07:20:37Z'
  curator: claude
  action: FIX_NODE_GROUNDING_CURIE
  changes: Overwrote 1 causal-node grounding(s) (obsolete/wrong GO -> corrected, verified
    vs OAK).
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: ENRICH_CAUSAL_GRAPH
  changes: Added 11 evidence-backed generic edges (12 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-24T17:21:12Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 7 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (biolink:catalyzes×2, METPO:2000202×2, biolink:produces×2, biolink:participates_in×1).
  llm_assisted: true
- timestamp: '2026-06-24T17:21:18Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv
    (UniProtKB:A0A081KVG3×1, UniProtKB:A0A415TT77×1).
  llm_assisted: true
- timestamp: '2026-06-26T07:15:18Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (UniProtKB:A0A016XII7×1).
  llm_assisted: true