3-hydroxypropionate/4-hydroxybutyrate cycle

traitmech:000024 · CLASS · REVIEWED

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.

3HP/4HB cycle fixes bicarbonate in aerobic Crenarchaeota

Evidence-backed causal sketch linking bicarbonate fixation via 3-hydroxypropionate and 4-hydroxybutyrate intermediates in Sulfolobales.

3HP/4HB cycle fixes bicarbonate in aerobic Crenarchaeota Interactive directed graph showing evidence-backed causal relationships for 3-hydroxypropionate/4-hydroxybutyrate cycle.

Edge evidence

  • hydrogencarbonate fixed by 3-hydroxypropionate/4-hydroxybutyrate cycle METPO:2007404

    Two molecules of bicarbonate are fixed per cycle turn.

    • DOI:10.1126/science.1149976 Berg et al. describe the 3HP/4HB cycle in Sulfolobales.
  • 3-hydroxypropionate/4-hydroxybutyrate cycle contributes to carbon fixation RO:0002326

    The 3HP/4HB cycle is among the six recognized autotrophic pathways.

    • DOI:10.1128/AEM.02473-10 Berg situates the 3HP/4HB cycle among recognized carbon-fixation pathways.
  • 3-hydroxypropionate/4-hydroxybutyrate cycle produces acetyl-CoA METPO:2000202

    A complete cycle turn fixes two bicarbonate to produce one acetyl-CoA.

    • DOI:10.1186/s40643-023-00705-9 A complete 3HP/4HB cycle fixes two HCO3- to produce one acetyl-CoA.
  • 3-hydroxypropionate/4-hydroxybutyrate cycle forms intermediate succinyl-CoA

    Carboxylation of acetyl-CoA/propionyl-CoA yields succinyl-CoA from two bicarbonate.

    • DOI:10.1186/s40643-023-00705-9 The pathway carboxylates acetyl-CoA/propionyl-CoA to form succinyl-CoA from two HCO3-.
  • succinyl-CoA is reduced to 4-hydroxybutyrate

    Succinyl-CoA is reduced to 4-hydroxybutyrate.

    • DOI:10.1186/s40643-023-00705-9 Succinyl-CoA is reduced to 4-hydroxybutyrate.
  • 4-hydroxybutyryl-CoA dehydratase dehydrates 4-hydroxybutyryl-CoA

    4-hydroxybutyryl-CoA is dehydrated to crotonyl-CoA.

    • DOI:10.1038/s42003-024-06432-x The cycle dehydrates 4-hydroxybutyryl-CoA to crotonyl-CoA.
  • 4-hydroxybutyryl-CoA dehydratase produces crotonyl-CoA METPO:2000202

    Dehydration of 4-hydroxybutyryl-CoA yields crotonyl-CoA.

    • DOI:10.1038/s42003-024-06432-x The pathway diagram shows dehydration to crotonyl-CoA.
  • crotonyl-CoA regenerates acetyl-CoA

    Crotonyl-CoA is processed/cleaved to regenerate acetyl-CoA for further cycle turns.

    • DOI:10.1186/s40643-023-00705-9 The pathway finally cleaves to yield acetyl-CoA for further turns.
  • NADPH is required by 3-hydroxypropionate/4-hydroxybutyrate cycle

    Reductive steps of the cycle consume NADPH (about four NADPH per turn).

    • DOI:10.1186/s40643-023-00705-9 Five reactions in the cycle require oxidation of NADPH; full cycle consumes four NADPH.
  • acetyl-CoA/propionyl-CoA carboxylase mediates carboxylation in 3-hydroxypropionate/4-hydroxybutyrate cycle

    Acetyl-CoA/propionyl-CoA carboxylase is the primary carboxylase fixing inorganic carbon.

    • DOI:10.1038/s42003-024-06432-x The cycle fixes CO2 onto acetyl-CoA via an acetyl-CoA/propionyl-CoA carboxylase, the primary carboxylase.

Provenance

Source
METPO (2025-11-25)
Definition source
DOI:10.1126/science.1149976

Synonyms (1)

  • 3HP/4HB cycle RELATED_SYNONYM · DOI:10.1126/science.1149976

kg-microbe context

Matched 1 kg-microbe node via parent_proxy.

  • METPO:1000060 [-1.052, -1.766, -1.194, +0.291, …]

512-dim DeepWalkSkipGramEnsmallen embedding from kg-microbe (2026-04-25).

Nearest neighbors in embedding space

Top-8 cosine-similar METPO traits from the 2026-04-25 deepwalk (512-D).

Curation history

  1. · PROPOSED_FROM_RESEARCH · claude

    Proposed candidate METABOLISM trait (3-hydroxypropionate/4-hydroxybutyrate cycle); archaeal sub-variant of carbon fixation.

  2. · CURATED_CAUSAL_GRAPH · claude

    Added evidence-backed causal graph (3HP/4HB Sulfolobales bicarbonate fixation) with CHEBI/GO node groundings and RO/METPO predicate groundings; promoted PROPOSED to REVIEWED.

  3. · ENRICH_CAUSAL_GRAPH · claude

    Added 8 evidence-backed generic edges (8 new nodes) from the deep-research report.

  4. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2000202×2).

  5. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:16474×1).

  6. · GROUND_CAUSAL_NODES · claude

    Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:16724×1, CHEBI:28522×1).

  7. · GROUND_CAUSAL_NODES · claude

    Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A650CEQ7×1, UniProtKB:A0A017H5F8×1).