identifier: traitmech:000023
label: 3-hydroxypropionate bicycle
definition: An autotrophic carbon-fixation pathway in which two molecules of bicarbonate
  are fixed via 3-hydroxypropionate and converted to glyoxylate and pyruvate. It is
  characteristic of the filamentous anoxygenic phototroph Chloroflexus aurantiacus.
definition_source: DOI:10.1128/AEM.02473-10
trait_category: METABOLISM
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- traitmech:000019
synonyms:
- synonym_text: 3-hydroxypropionate 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 3-hydroxypropionate bicycle and its association
    with Chloroflexus.
- reference: DOI:10.1146/annurev-marine-120709-142712
  notes: Hügler & Sievert include the 3-hydroxypropionate pathway among autotrophic
    carbon-fixation strategies.
canonical_examples:
- taxon_id: NCBITaxon:1108
  taxon_label: Chloroflexus aurantiacus
  note: "Where the 3-hydroxypropionate bicycle of autotrophic CO2 fixation was discovered (filamentous anoxygenic phototroph)."
  reference: PMID:19955419
causal_graphs:
- graph_id: three_hp_bicycle_chloroflexus
  title: 3-hydroxypropionate bicycle fixes bicarbonate in Chloroflexus
  description: Evidence-backed causal sketch linking bicarbonate fixation via 3-hydroxypropionate
    to glyoxylate and pyruvate in Chloroflexus aurantiacus.
  nodes:
  - node_id: three_hp_bicycle_trait
    label: 3-hydroxypropionate bicycle
    node_type: TRAIT
    grounding: traitmech:000023
    description: Autotrophic carbon-fixation bicycle via 3-hydroxypropionate.
  - node_id: bicarbonate
    label: hydrogencarbonate
    node_type: CHEMICAL
    grounding: CHEBI:17544
    description: Inorganic carbon substrate fixed by the bicycle.
  - 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: acetyl_coa_carboxylase
    label: acetyl-CoA carboxylase
    node_type: GENE_OR_PROTEIN
    description: EC 6.4.1.2; carboxylates acetyl-CoA to malonyl-CoA using bicarbonate
      and ATP.
    grounding: UniProtKB:A0A059L760
  - node_id: malonyl_coa
    label: malonyl-CoA
    node_type: CHEMICAL
    description: Product of acetyl-CoA carboxylation; substrate for malonyl-CoA reductase.
  - node_id: propionyl_coa_carboxylase
    label: propionyl-CoA carboxylase
    node_type: GENE_OR_PROTEIN
    description: EC 6.4.1.3; carboxylates propionyl-CoA to (2S)-methylmalonyl-CoA
      using bicarbonate and ATP.
    grounding: UniProtKB:A0A024E6S7
  - node_id: methylmalonyl_coa
    label: (2S)-methylmalonyl-CoA
    node_type: CHEMICAL
    description: Product of propionyl-CoA carboxylation in the second carboxylation
      step.
  - node_id: malonyl_coa_reductase
    label: malonyl-CoA reductase
    node_type: GENE_OR_PROTEIN
    description: EC 1.2.1.75; diagnostic enzyme reducing malonyl-CoA to 3-hydroxypropionate.
    grounding: UniProtKB:Q6QQP7
  - node_id: three_hydroxypropionate
    label: 3-hydroxypropionate
    node_type: CHEMICAL
    description: Signature intermediate of the bicycle, produced by malonyl-CoA reductase.
    grounding: CHEBI:16510
  - node_id: propionyl_coa_synthase
    label: propionyl-CoA synthase
    node_type: GENE_OR_PROTEIN
    description: Multifunctional enzyme converting 3-hydroxypropionate to propionyl-CoA.
  - node_id: propionyl_coa
    label: propionyl-CoA
    node_type: CHEMICAL
    description: Product of propionyl-CoA synthase; substrate for the second carboxylation.
    grounding: CHEBI:15539
  - node_id: mmc_lyase
    label: MMC lyase
    node_type: GENE_OR_PROTEIN
    description: Multifunctional malyl-CoA/citramalyl-CoA lyase cleaving citramalyl-CoA
      to pyruvate and acetyl-CoA.
  - node_id: pyruvate
    label: pyruvate
    node_type: CHEMICAL
    description: Net organic carbon output of the bicycle.
    grounding: CHEBI:15361
  - node_id: acetyl_coa
    label: acetyl-CoA
    node_type: CHEMICAL
    description: Co-product released during the cycle and regenerated as starting
      carboxylation substrate.
  edges:
  - subject: bicarbonate
    predicate: fixed by
    object: three_hp_bicycle_trait
    description: Two molecules of bicarbonate are fixed per cycle turn.
    evidence:
    - reference: DOI:10.1128/AEM.02473-10
      notes: Berg describes the 3-hydroxypropionate bicycle in Chloroflexus.
    predicate_id: METPO:2007404
  - subject: three_hp_bicycle_trait
    predicate: contributes to
    object: carbon_fixation_process
    description: The bicycle is one of the recognized autotrophic CO2-fixation pathways.
    evidence:
    - reference: DOI:10.1146/annurev-marine-120709-142712
      notes: Hügler & Sievert include the 3-hydroxypropionate pathway among autotrophic
        carbon-fixation strategies.
    predicate_id: RO:0002326
  - subject: acetyl_coa_carboxylase
    predicate: causally upstream of
    object: malonyl_coa
    description: Acetyl-CoA carboxylase converts acetyl-CoA and bicarbonate to malonyl-CoA
      at the expense of ATP.
    evidence:
    - reference: DOI:10.17192/z2022.0467
      notes: acetyl-CoA carboxylase (EC 6.4.1.2) converts acetyl-CoA and bicarbonate
        to malonyl-CoA.
  - subject: propionyl_coa_carboxylase
    predicate: causally upstream of
    object: methylmalonyl_coa
    description: Propionyl-CoA carboxylase converts propionyl-CoA and bicarbonate
      to (2S)-methylmalonyl-CoA at the expense of ATP.
    evidence:
    - reference: DOI:10.17192/z2022.0467
      notes: propionyl-CoA carboxylase (EC 6.4.1.3) converts propionyl-CoA and bicarbonate
        to (2S)-methylmalonyl-CoA.
  - subject: malonyl_coa_reductase
    predicate: causally upstream of
    object: three_hydroxypropionate
    description: Malonyl-CoA reductase reduces malonyl-CoA to 3-hydroxypropionate;
      central diagnostic enzyme.
    evidence:
    - reference: DOI:10.1146/annurev-marine-120709-142712
      notes: malonyl-CoA reductase reducing malonyl-CoA to 3-hydroxypropionate.
  - subject: propionyl_coa_synthase
    predicate: causally upstream of
    object: propionyl_coa
    description: Propionyl-CoA synthase converts 3-hydroxypropionate to propionyl-CoA.
    evidence:
    - reference: DOI:10.1146/annurev-marine-120709-142712
      notes: propionyl-CoA synthase converting 3-hydroxypropionate to propionyl-CoA.
  - subject: mmc_lyase
    predicate: causally upstream of
    object: pyruvate
    description: MMC lyase cleaves citramalyl-CoA to pyruvate and acetyl-CoA.
    evidence:
    - reference: DOI:10.1146/annurev-marine-120709-142712
      notes: cleavage of citramalyl-CoA to pyruvate and acetyl-CoA.
  - subject: mmc_lyase
    predicate: causally upstream of
    object: acetyl_coa
    description: MMC lyase cleavage also yields acetyl-CoA alongside pyruvate.
    evidence:
    - reference: DOI:10.1146/annurev-marine-120709-142712
      notes: cleavage of citramalyl-CoA to pyruvate and acetyl-CoA.
  - subject: three_hp_bicycle_trait
    predicate: has output
    object: pyruvate
    description: Overall the bicycle produces one pyruvate from three bicarbonates.
    evidence:
    - reference: DOI:10.1146/annurev-marine-120709-142712
      notes: producing one pyruvate from three bicarbonates.
curation_history:
- timestamp: '2026-05-30T00:00:00Z'
  curator: claude
  action: PROPOSED_FROM_RESEARCH
  changes: Proposed candidate METABOLISM trait (3-hydroxypropionate bicycle); 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 (3HP bicycle bicarbonate 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 7 evidence-backed generic edges (11 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-24T17:23:33Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 3 causal-node grounding field(s) via mappings/node_grounding.tsv
    (CHEBI:16510×1, CHEBI:15539×1, CHEBI:15361×1).
  llm_assisted: true
- timestamp: '2026-06-26T07:15:19Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 3 causal-node grounding field(s) via mappings/node_grounding.tsv
    (UniProtKB:A0A059L760×1, UniProtKB:A0A024E6S7×1, UniProtKB:Q6QQP7×1).
  llm_assisted: true