identifier: traitmech:000022
label: Wood-Ljungdahl pathway
definition: An autotrophic carbon-fixation pathway (the reductive acetyl-CoA pathway)
  in which two molecules of CO2 are reduced and combined into acetyl-CoA. It is energetically
  efficient and used by acetogenic bacteria, methanogenic archaea, and some sulfate-reducing
  bacteria.
definition_source: DOI:10.1016/j.bbapap.2008.08.012
trait_category: METABOLISM
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- traitmech:000019
synonyms:
- synonym_text: reductive acetyl-CoA pathway
  synonym_type: EXACT_SYNONYM
  source: DOI:10.1016/j.bbapap.2008.08.012
evidence:
- reference: DOI:10.1016/j.bbapap.2008.08.012
  notes: Ragsdale & Pierce, "Acetogenesis and the Wood-Ljungdahl pathway of CO2 fixation",
    is the reference treatment of this reductive acetyl-CoA pathway.
- reference: DOI:10.1128/AEM.02473-10
  notes: Berg review places the reductive acetyl-CoA (Wood-Ljungdahl) pathway among
    the recognized autotrophic carbon-fixation pathways.
canonical_examples:
- taxon_id: NCBITaxon:1525
  taxon_label: Neomoorella thermoacetica
  note: "Model acetogen used to elucidate the reductive acetyl-CoA / Wood-Ljungdahl pathway (formerly Moorella/Clostridium thermoaceticum)."
  reference: https://pmc.ncbi.nlm.nih.gov/articles/PMC2575129/
causal_graphs:
- graph_id: wood_ljungdahl_reductive_acetyl_coa
  title: Wood-Ljungdahl pathway reduces 2 CO2 to acetyl-CoA
  description: Evidence-backed causal sketch linking reduction of two CO2 molecules
    into acetyl-CoA via the reductive acetyl-CoA pathway.
  nodes:
  - node_id: wood_ljungdahl_trait
    label: Wood-Ljungdahl pathway
    node_type: TRAIT
    grounding: traitmech:000022
    description: Reductive acetyl-CoA pathway combining 2 CO2 into acetyl-CoA.
  - node_id: wood_ljungdahl_pathway
    label: Wood-Ljungdahl pathway
    node_type: PATHWAY
    grounding: GO:0030634
    description: Acetyl-CoA biosynthetic process from carbon dioxide.
  - node_id: carbon_dioxide
    label: carbon dioxide
    node_type: CHEMICAL
    grounding: CHEBI:16526
    description: Inorganic carbon substrate reduced to acetyl-CoA.
  - node_id: methyl_branch
    label: methyl branch
    node_type: PATHWAY
    description: Eastern branch of WLP reducing CO2 stepwise to methyl-tetrahydrofolate.
  - node_id: carbonyl_branch
    label: carbonyl branch
    node_type: PATHWAY
    description: Western branch of WLP reducing CO2 to CO at the CODH/ACS complex.
  - node_id: formate_dehydrogenase
    label: formate dehydrogenase (FDH)
    node_type: GENE_OR_PROTEIN
    description: Enzyme reducing CO2 to formate, the first step of the WLP methyl
      branch.
  - node_id: formate
    label: formate
    node_type: CHEMICAL
    description: C1 intermediate produced by reduction of CO2 in the methyl branch.
  - node_id: formyl_thf_synthetase
    label: formyl-THF synthetase (FTS/Fhs)
    node_type: GENE_OR_PROTEIN
    description: Enzyme forming formyl-THF from formate, consuming one ATP.
  - node_id: atp
    label: ATP
    node_type: CHEMICAL
    description: Adenosine triphosphate consumed during formate activation in the
      WLP.
  - node_id: methyltransferase
    label: methyltransferase
    node_type: GENE_OR_PROTEIN
    description: Enzyme transferring the methyl group onto the corrinoid iron-sulfur
      protein.
    grounding: UniProtKB:A0A0C5IX96
  - node_id: cofesp
    label: corrinoid iron-sulfur protein (CoFeSP)
    node_type: GENE_OR_PROTEIN
    description: Corrinoid iron-sulfur protein carrying the methyl group to ACS.
  - node_id: acetyl_coa_synthase
    label: acetyl-CoA synthase (ACS)
    node_type: GENE_OR_PROTEIN
    description: Enzyme condensing CO, methyl-CoFeSP and CoA into acetyl-CoA.
  - node_id: acetyl_coa
    label: acetyl-CoA
    node_type: CHEMICAL
    description: Central product of the WLP, the convergence point of both branches.
  - node_id: tetrahydrofolate
    label: tetrahydrofolate (THF)
    node_type: CHEMICAL
    description: C1 carrier cofactor of the WLP methyl branch.
  - node_id: net_zero_atp_slp
    label: zero net ATP from substrate-level phosphorylation
    node_type: QUALITY
    description: 'Energetic property: formate activation offsets SLP so the WLP nets
      zero ATP.'
  edges:
  - subject: wood_ljungdahl_pathway
    predicate: enables
    object: wood_ljungdahl_trait
    description: The reductive acetyl-CoA pathway underlies the trait.
    evidence:
    - reference: DOI:10.1016/j.bbapap.2008.08.012
      notes: Ragsdale & Pierce review the Wood-Ljungdahl pathway as the reference
        reductive acetyl-CoA pathway.
    predicate_id: RO:0002327
  - subject: carbon_dioxide
    predicate: fixed by
    object: wood_ljungdahl_trait
    description: Two molecules of CO2 are fixed and combined into acetyl-CoA.
    evidence:
    - reference: DOI:10.1128/AEM.02473-10
      notes: Berg places Wood-Ljungdahl among the recognized autotrophic carbon-fixation
        pathways.
    predicate_id: METPO:2007404
  - subject: wood_ljungdahl_pathway
    predicate: has part
    object: methyl_branch
    description: The WLP comprises a methyl (eastern) branch.
    evidence:
    - reference: DOI:10.3389/fbioe.2024.1395540
      notes: 'The Wood-Ljungdahl pathway is a two-branch autotrophic CO2 fixation
        pathway: a methyl branch and a carbonyl branch.'
  - subject: wood_ljungdahl_pathway
    predicate: has part
    object: carbonyl_branch
    description: The WLP comprises a carbonyl (western) branch.
    evidence:
    - reference: DOI:10.3389/fbioe.2024.1395540
      notes: The Wood-Ljungdahl pathway is a two-branch autotrophic CO2 fixation pathway
        with a carbonyl branch.
  - subject: formate_dehydrogenase
    predicate: reduces
    object: carbon_dioxide
    description: 'FDH reduces CO2 to formate, the first methyl-branch step (product:
      formate node).'
    evidence:
    - reference: DOI:10.3389/fbioe.2024.1395540
      notes: Formate dehydrogenase (FDH) reduces CO2 to formate; canonical bacterial
        WLP step.
    predicate_id: METPO:2000017
  - subject: formate_dehydrogenase
    predicate: produces
    object: formate
    description: FDH-catalyzed reduction of CO2 yields formate.
    evidence:
    - reference: DOI:10.3389/fbioe.2024.1395540
      notes: Formate dehydrogenase (FDH) reduces CO2 to formate.
    predicate_id: METPO:2000202
  - subject: formyl_thf_synthetase
    predicate: requires
    object: atp
    description: Formyl-THF synthetase consumes one ATP to activate formate.
    evidence:
    - reference: DOI:10.3389/fbioe.2024.1395540
      notes: Formyl-THF synthetase (FTS) forms formyl-THF, consuming one ATP.
  - subject: methyltransferase
    predicate: transfers methyl to
    object: cofesp
    description: Methyltransferase transfers the methyl group onto the corrinoid iron-sulfur
      protein.
    evidence:
    - reference: DOI:10.3389/fbioe.2024.1395540
      notes: Methyltransferase transfers the methyl onto a corrinoid iron-sulfur protein
        (CoFeSP).
  - subject: acetyl_coa_synthase
    predicate: produces
    object: acetyl_coa
    description: ACS condenses CO, methyl-CoFeSP and CoA into acetyl-CoA, the terminal
      WLP step.
    evidence:
    - reference: DOI:10.3389/fbioe.2024.1395540
      notes: ACS combines CO, methyl-CoFeSP and CoA into acetyl-CoA; central terminal
        step of WLP.
    predicate_id: METPO:2000202
  - subject: tetrahydrofolate
    predicate: functions as C1 carrier in
    object: methyl_branch
    description: THF serves as the C1 carrier of the WLP methyl branch.
    evidence:
    - reference: DOI:10.1039/d4cb00099d
      notes: WLP converts two CO2 to one acetyl-CoA using THF as the C1 carrier.
  - subject: wood_ljungdahl_pathway
    predicate: has quality
    object: net_zero_atp_slp
    description: Formate activation offsets SLP so the WLP nets zero ATP by substrate-level
      phosphorylation.
    evidence:
    - reference: DOI:10.3389/fbioe.2024.1395540
      notes: Activation of formate consumes one ATP, so substrate-level phosphorylation
        nets zero ATP.
curation_history:
- timestamp: '2026-05-30T00:00:00Z'
  curator: claude
  action: PROPOSED_FROM_RESEARCH
  changes: Proposed candidate METABOLISM trait (Wood-Ljungdahl / reductive acetyl-CoA
    carbon-fixation pathway); sub-variant of carbon fixation. Distinct from the existing
    acetogenesis metabolism class (which produces acetate via this pathway).
  llm_assisted: true
- timestamp: '2026-06-10T14:00:00Z'
  curator: claude
  action: CURATED_CAUSAL_GRAPH
  changes: Added evidence-backed causal graph (Wood-Ljungdahl reductive acetyl-CoA)
    with GO/CHEBI node groundings and RO/METPO predicate groundings; promoted PROPOSED
    to REVIEWED.
  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 9 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 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2000202×2, METPO:2000017×1).
  llm_assisted: true
- timestamp: '2026-06-26T07:15:19Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (UniProtKB:A0A0C5IX96×1).
  llm_assisted: true