identifier: traitmech:000024 label: 3-hydroxypropionate/4-hydroxybutyrate cycle definition: An autotrophic carbon-fixation pathway that fixes two molecules of bicarbonate per turn via 3-hydroxypropionate and 4-hydroxybutyrate intermediates. It operates in aerobic and microaerophilic Crenarchaeota such as Sulfolobus and Metallosphaera. definition_source: DOI:10.1126/science.1149976 trait_category: METABOLISM term_kind: CLASS mapping_status: REVIEWED parent_traits: - traitmech:000019 synonyms: - synonym_text: 3HP/4HB cycle synonym_type: RELATED_SYNONYM source: DOI:10.1126/science.1149976 evidence: - reference: DOI:10.1126/science.1149976 notes: Berg et al. described the 3-hydroxypropionate/4-hydroxybutyrate autotrophic CO2-assimilation pathway in Archaea (Sulfolobales). - reference: DOI:10.1128/AEM.02473-10 notes: Berg review situates the 3HP/4HB cycle among the six recognized autotrophic carbon-fixation pathways. canonical_examples: - taxon_id: NCBITaxon:43687 taxon_label: Metallosphaera sedula note: "Thermoacidophilic crenarchaeon where the 3-hydroxypropionate/4-hydroxybutyrate CO2-fixation cycle was characterized." reference: PMID:18079405 causal_graphs: - graph_id: three_hp_four_hb_sulfolobales title: 3HP/4HB cycle fixes bicarbonate in aerobic Crenarchaeota description: Evidence-backed causal sketch linking bicarbonate fixation via 3-hydroxypropionate and 4-hydroxybutyrate intermediates in Sulfolobales. nodes: - node_id: three_hp_four_hb_trait label: 3-hydroxypropionate/4-hydroxybutyrate cycle node_type: TRAIT grounding: traitmech:000024 description: Archaeal autotrophic carbon-fixation cycle. - node_id: bicarbonate label: hydrogencarbonate node_type: CHEMICAL grounding: CHEBI:17544 description: Inorganic carbon substrate fixed by the cycle. - 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 label: acetyl-CoA node_type: CHEMICAL description: Central product/regenerated CoA-thioester of the cycle. - node_id: succinyl_coa label: succinyl-CoA node_type: CHEMICAL description: Central CoA-thioester intermediate of the 3HP/4HB cycle. - node_id: four_hydroxybutyrate label: 4-hydroxybutyrate node_type: CHEMICAL description: Defining 4-hydroxybutyrate intermediate of the cycle. grounding: CHEBI:16724 - node_id: crotonyl_coa label: crotonyl-CoA node_type: CHEMICAL description: CoA-thioester intermediate formed by 4-hydroxybutyryl-CoA dehydration. - node_id: four_hydroxybutyryl_coa label: 4-hydroxybutyryl-CoA node_type: CHEMICAL description: Activated CoA-thioester of 4-hydroxybutyrate. grounding: CHEBI:28522 - node_id: nadph label: NADPH node_type: CHEMICAL description: Reducing cofactor consumed by reductive steps of the cycle. grounding: CHEBI:16474 - node_id: acetyl_propionyl_coa_carboxylase label: acetyl-CoA/propionyl-CoA carboxylase node_type: GENE_OR_PROTEIN description: Primary carboxylase fixing inorganic carbon in the cycle. grounding: UniProtKB:A0A650CEQ7 - node_id: four_hydroxybutyryl_coa_dehydratase label: 4-hydroxybutyryl-CoA dehydratase node_type: GENE_OR_PROTEIN description: Enzyme dehydrating 4-hydroxybutyryl-CoA to crotonyl-CoA. grounding: UniProtKB:A0A017H5F8 edges: - subject: bicarbonate predicate: fixed by object: three_hp_four_hb_trait description: Two molecules of bicarbonate are fixed per cycle turn. evidence: - reference: DOI:10.1126/science.1149976 notes: Berg et al. describe the 3HP/4HB cycle in Sulfolobales. predicate_id: METPO:2007404 - subject: three_hp_four_hb_trait predicate: contributes to object: carbon_fixation_process description: The 3HP/4HB cycle is among the six recognized autotrophic pathways. evidence: - reference: DOI:10.1128/AEM.02473-10 notes: Berg situates the 3HP/4HB cycle among recognized carbon-fixation pathways. predicate_id: RO:0002326 - subject: three_hp_four_hb_trait predicate: produces object: acetyl_coa description: A complete cycle turn fixes two bicarbonate to produce one acetyl-CoA. evidence: - reference: DOI:10.1186/s40643-023-00705-9 notes: A complete 3HP/4HB cycle fixes two HCO3- to produce one acetyl-CoA. predicate_id: METPO:2000202 - subject: three_hp_four_hb_trait predicate: forms intermediate object: succinyl_coa description: Carboxylation of acetyl-CoA/propionyl-CoA yields succinyl-CoA from two bicarbonate. evidence: - reference: DOI:10.1186/s40643-023-00705-9 notes: The pathway carboxylates acetyl-CoA/propionyl-CoA to form succinyl-CoA from two HCO3-. - subject: succinyl_coa predicate: is reduced to object: four_hydroxybutyrate description: Succinyl-CoA is reduced to 4-hydroxybutyrate. evidence: - reference: DOI:10.1186/s40643-023-00705-9 notes: Succinyl-CoA is reduced to 4-hydroxybutyrate. - subject: four_hydroxybutyryl_coa_dehydratase predicate: dehydrates object: four_hydroxybutyryl_coa description: 4-hydroxybutyryl-CoA is dehydrated to crotonyl-CoA. evidence: - reference: DOI:10.1038/s42003-024-06432-x notes: The cycle dehydrates 4-hydroxybutyryl-CoA to crotonyl-CoA. - subject: four_hydroxybutyryl_coa_dehydratase predicate: produces object: crotonyl_coa description: Dehydration of 4-hydroxybutyryl-CoA yields crotonyl-CoA. evidence: - reference: DOI:10.1038/s42003-024-06432-x notes: The pathway diagram shows dehydration to crotonyl-CoA. predicate_id: METPO:2000202 - subject: crotonyl_coa predicate: regenerates object: acetyl_coa description: Crotonyl-CoA is processed/cleaved to regenerate acetyl-CoA for further cycle turns. evidence: - reference: DOI:10.1186/s40643-023-00705-9 notes: The pathway finally cleaves to yield acetyl-CoA for further turns. - subject: nadph predicate: is required by object: three_hp_four_hb_trait description: Reductive steps of the cycle consume NADPH (about four NADPH per turn). evidence: - reference: DOI:10.1186/s40643-023-00705-9 notes: Five reactions in the cycle require oxidation of NADPH; full cycle consumes four NADPH. - subject: acetyl_propionyl_coa_carboxylase predicate: mediates carboxylation in object: three_hp_four_hb_trait description: Acetyl-CoA/propionyl-CoA carboxylase is the primary carboxylase fixing inorganic carbon. evidence: - reference: DOI:10.1038/s42003-024-06432-x notes: The cycle fixes CO2 onto acetyl-CoA via an acetyl-CoA/propionyl-CoA carboxylase, the primary carboxylase. curation_history: - timestamp: '2026-05-30T00:00:00Z' curator: claude action: PROPOSED_FROM_RESEARCH changes: Proposed candidate METABOLISM trait (3-hydroxypropionate/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 (3HP/4HB Sulfolobales 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 8 evidence-backed generic edges (8 new nodes) from the deep-research report. llm_assisted: true - timestamp: '2026-06-24T17:21:12Z' 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: '2026-06-24T17:21:19Z' curator: claude action: GROUND_CAUSAL_NODES changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:16474×1). llm_assisted: true - timestamp: '2026-06-24T17:23:33Z' curator: claude action: GROUND_CAUSAL_NODES changes: Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:16724×1, CHEBI:28522×1). llm_assisted: true - timestamp: '2026-06-26T07:15:19Z' curator: claude action: GROUND_CAUSAL_NODES changes: Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A650CEQ7×1, UniProtKB:A0A017H5F8×1). llm_assisted: true