identifier: traitmech:000025
label: dicarboxylate/4-hydroxybutyrate cycle
definition: An autotrophic carbon-fixation pathway that fixes one molecule of CO2
  and one of bicarbonate per turn via a dicarboxylate stage and a 4-hydroxybutyrate
  stage. It operates in anaerobic and microaerophilic Crenarchaeota such as Ignicoccus
  and Thermoproteales.
definition_source: DOI:10.1126/science.1149976
trait_category: METABOLISM
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- traitmech:000019
synonyms:
- synonym_text: DC/4HB cycle
  synonym_type: RELATED_SYNONYM
  source: DOI:10.1128/AEM.02473-10
evidence:
- reference: DOI:10.1128/AEM.02473-10
  notes: Berg review describes the dicarboxylate/4-hydroxybutyrate cycle as the anaerobic
    archaeal counterpart of the 3HP/4HB cycle.
- reference: DOI:10.1126/science.1149976
  notes: Berg et al.'s archaeal carbon-fixation work establishes the 4-hydroxybutyrate
    chemistry shared by this cycle in Crenarchaeota.
canonical_examples:
- taxon_id: NCBITaxon:160233
  taxon_label: Ignicoccus hospitalis
  note: "Hyperthermophilic crenarchaeon in which the dicarboxylate/4-hydroxybutyrate autotrophic CO2-fixation cycle was discovered."
  reference: PMID:18511565
causal_graphs:
- graph_id: dc_four_hb_anaerobic_archaeal_co2_fixation
  title: DC/4HB cycle fixes CO2 in anaerobic Crenarchaeota
  description: Evidence-backed causal sketch linking dicarboxylate and 4-hydroxybutyrate
    intermediates to CO2 fixation in anaerobic / microaerophilic Crenarchaeota.
  nodes:
  - node_id: dc_four_hb_trait
    label: dicarboxylate/4-hydroxybutyrate cycle
    node_type: TRAIT
    grounding: traitmech:000025
    description: Anaerobic archaeal autotrophic carbon-fixation cycle.
  - node_id: carbon_dioxide
    label: carbon dioxide
    node_type: CHEMICAL
    grounding: CHEBI:16526
    description: One CO2 and one bicarbonate fixed per cycle turn.
  - node_id: carbon_fixation_process
    label: carbon fixation
    node_type: BIOLOGICAL_PROCESS
    grounding: GO:0015977
    description: Conversion of inorganic carbon into organic compounds.
  - node_id: molecular_oxygen
    label: molecular oxygen
    node_type: CHEMICAL
    description: O2; inactivates O2-sensitive enzymes and electron carriers of the
      cycle.
    grounding: CHEBI:15379
  - node_id: bicarbonate
    label: bicarbonate
    node_type: CHEMICAL
    description: HCO3-; inorganic carbon species used as a carboxylation cosubstrate.
    grounding: CHEBI:17544
  - node_id: pyruvate_synthase
    label: pyruvate synthase (pyruvate:ferredoxin oxidoreductase)
    node_type: GENE_OR_PROTEIN
    description: Reductively carboxylates acetyl-CoA to pyruvate using CO2.
  - node_id: pep_carboxylase
    label: phosphoenolpyruvate carboxylase
    node_type: GENE_OR_PROTEIN
    description: Carboxylates PEP to oxaloacetate using bicarbonate.
    grounding: UniProtKB:A0A031JWX5
  - node_id: acetyl_coa
    label: acetyl-CoA
    node_type: CHEMICAL
    description: Starting and regenerated C2 acceptor of the cycle.
  - node_id: pyruvate
    label: pyruvate
    node_type: CHEMICAL
    description: Product of reductive carboxylation of acetyl-CoA.
    grounding: CHEBI:15361
  - node_id: phosphoenolpyruvate
    label: phosphoenolpyruvate
    node_type: CHEMICAL
    description: Substrate for carboxylation to oxaloacetate.
  - node_id: oxaloacetate
    label: oxaloacetate
    node_type: CHEMICAL
    description: C4 product of PEP carboxylation in the dicarboxylate stage.
    grounding: CHEBI:16452
  - node_id: four_hydroxybutyryl_coa
    label: 4-hydroxybutyryl-CoA
    node_type: CHEMICAL
    description: Substrate of the hallmark radical dehydratase in the 4HB branch.
    grounding: CHEBI:28522
  - node_id: four_hydroxybutyryl_coa_dehydratase
    label: 4-hydroxybutyryl-CoA dehydratase
    node_type: GENE_OR_PROTEIN
    description: Hallmark radical enzyme dehydrating 4-hydroxybutyryl-CoA to crotonyl-CoA.
    grounding: UniProtKB:A0A017H5F8
  - node_id: crotonyl_coa
    label: crotonyl-CoA
    node_type: CHEMICAL
    description: Product of the radical dehydratase; cleaved via beta-oxidation to
      two acetyl-CoA.
  edges:
  - subject: carbon_dioxide
    predicate: fixed by
    object: dc_four_hb_trait
    description: CO2 is fixed by the anaerobic archaeal DC/4HB cycle.
    evidence:
    - reference: DOI:10.1128/AEM.02473-10
      notes: Berg describes the DC/4HB cycle as the anaerobic counterpart of the 3HP/4HB
        cycle.
    predicate_id: METPO:2007404
  - subject: dc_four_hb_trait
    predicate: contributes to
    object: carbon_fixation_process
    description: The DC/4HB cycle is one of the recognized autotrophic CO2 pathways.
    evidence:
    - reference: DOI:10.1126/science.1149976
      notes: Berg et al. establish 4-hydroxybutyrate chemistry shared by the cycle
        in Crenarchaeota.
    predicate_id: RO:0002326
  - subject: molecular_oxygen
    predicate: negatively regulates
    object: dc_four_hb_trait
    description: O2 constrains the cycle because key enzymes and electron carriers
      are oxygen-sensitive, restricting it to anoxic conditions.
    evidence:
    - reference: DOI:10.1128/AEM.02473-10
      notes: Restricted to organisms growing under anoxic conditions due to oxygen
        sensitivity of key enzymes and electron carriers.
  - subject: carbon_dioxide
    predicate: is cosubstrate for
    object: pyruvate_synthase
    description: CO2 serves as the carboxylation cosubstrate for pyruvate synthase
      in the cycle.
    evidence:
    - reference: DOI:10.1002/9783527629916
      notes: CO2 as cosubstrate for pyruvate synthase.
  - subject: bicarbonate
    predicate: is cosubstrate for
    object: pep_carboxylase
    description: Bicarbonate is the inorganic carbon cosubstrate for PEP carboxylase,
      supporting mixed CO2/HCO3- usage.
    evidence:
    - reference: DOI:10.1002/9783527629916
      notes: Bicarbonate as cosubstrate for PEP carboxylase.
  - subject: pyruvate_synthase
    predicate: catalyzes conversion of
    object: acetyl_coa
    description: Pyruvate synthase reductively carboxylates acetyl-CoA to pyruvate,
      the first fixation step.
    evidence:
    - reference: DOI:10.1002/9783527629916
      notes: Starts from acetyl-CoA, which is reductively carboxylated to pyruvate.
  - subject: pyruvate_synthase
    predicate: produces
    object: pyruvate
    description: Reductive carboxylation of acetyl-CoA by pyruvate synthase yields
      pyruvate.
    evidence:
    - reference: DOI:10.1002/9783527629916
      notes: Acetyl-CoA is reductively carboxylated to pyruvate.
    predicate_id: METPO:2000202
  - subject: pep_carboxylase
    predicate: catalyzes conversion of
    object: phosphoenolpyruvate
    description: PEP carboxylase carboxylates phosphoenolpyruvate to oxaloacetate
      in the dicarboxylate stage.
    evidence:
    - reference: DOI:10.1002/9783527629916
      notes: Pyruvate is converted to PEP and then carboxylated to oxaloacetate.
  - subject: pep_carboxylase
    predicate: produces
    object: oxaloacetate
    description: Carboxylation of PEP by PEP carboxylase yields oxaloacetate.
    evidence:
    - reference: DOI:10.1002/9783527629916
      notes: PEP is carboxylated to oxaloacetate.
    predicate_id: METPO:2000202
  - subject: four_hydroxybutyryl_coa_dehydratase
    predicate: catalyzes conversion of
    object: four_hydroxybutyryl_coa
    description: Hallmark radical 4-hydroxybutyryl-CoA dehydratase dehydrates 4-hydroxybutyryl-CoA
      to crotonyl-CoA.
    evidence:
    - reference: DOI:10.1073/pnas.0801043105
      notes: Dehydrated by a radical 4-hydroxybutyryl-CoA dehydratase to crotonyl-CoA;
        core hallmark enzyme of the 4HB branch.
  - subject: four_hydroxybutyryl_coa_dehydratase
    predicate: produces
    object: crotonyl_coa
    description: The radical dehydratase yields crotonyl-CoA in the 4-hydroxybutyrate
      branch.
    evidence:
    - reference: DOI:10.1073/pnas.0801043105
      notes: Dehydrated to crotonyl-CoA.
    predicate_id: METPO:2000202
  - subject: crotonyl_coa
    predicate: is converted via beta-oxidation to
    object: acetyl_coa
    description: Crotonyl-CoA is cleaved via beta-oxidation to regenerate two acetyl-CoA,
      closing the cycle.
    evidence:
    - reference: DOI:10.1073/pnas.0801043105
      notes: Via beta-oxidation yields two acetyl-CoA.
curation_history:
- timestamp: '2026-05-30T00:00:00Z'
  curator: claude
  action: PROPOSED_FROM_RESEARCH
  changes: Proposed candidate METABOLISM trait (dicarboxylate/4-hydroxybutyrate cycle);
    archaeal sub-variant of carbon fixation.
  llm_assisted: true
- timestamp: '2026-06-10T14:00:00Z'
  curator: claude
  action: CURATED_CAUSAL_GRAPH
  changes: Added evidence-backed causal graph (DC/4HB anaerobic archaeal CO2 fixation)
    with CHEBI/GO node groundings and RO/METPO predicate groundings; promoted PROPOSED
    to REVIEWED.
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: ENRICH_CAUSAL_GRAPH
  changes: Added 10 evidence-backed generic edges (11 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-24T17:21:12Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2000202×3).
  llm_assisted: true
- timestamp: '2026-06-24T17:21:18Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (CHEBI:15379×1).
  llm_assisted: true
- timestamp: '2026-06-24T17:23:32Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 4 causal-node grounding field(s) via mappings/node_grounding.tsv
    (CHEBI:17544×1, CHEBI:15361×1, CHEBI:16452×1, CHEBI:28522×1).
  llm_assisted: true
- timestamp: '2026-06-26T07:15:18Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv
    (UniProtKB:A0A031JWX5×1, UniProtKB:A0A017H5F8×1).
  llm_assisted: true