Homoacetogenesis

METPO:1000846 · CLASS · REVIEWED

A metabolism in which acetate is produced as the sole reduced end product from reduction of CO2 via the acetyl-CoA pathway.

Homoacetogenesis Wood-Ljungdahl acetate mechanism

DOI-backed graph linking anaerobic CO2 reduction, hydrogen/CO inputs, acetyl-CoA synthesis, and acetate as the sole reduced product.

Homoacetogenesis Wood-Ljungdahl acetate mechanism Interactive directed graph showing evidence-backed causal relationships for Homoacetogenesis.

Edge evidence

  • Homoacetogenesis occurs in anaerobic condition biolink:occurs_in

    Homoacetogenesis is an anaerobic acetogenic metabolism.

    • DOI:10.1023/A:1020514617738 obligately anaerobic bacteria Supports anaerobic context for acetogens.
  • Homoacetogenesis has mechanistic pathway Wood-Ljungdahl pathway

    Homoacetogenesis proceeds through the Wood-Ljungdahl pathway.

    • DOI:10.1016/j.tibtech.2019.05.008 Wood-Ljungdahl pathway Supports pathway assignment for acetogens.
  • carbon dioxide participates in Wood-Ljungdahl pathway biolink:participates_in

    CO2 is reduced through the Wood-Ljungdahl pathway.

    • DOI:10.1016/j.tibtech.2019.05.008 carbon dioxide are reduced Supports CO2 as substrate.
  • molecular hydrogen provides electrons for Wood-Ljungdahl pathway METPO:2007402

    Hydrogen can provide reducing equivalents for CO2 reduction.

    • DOI:10.1016/j.bbapap.2008.08.012 acetyl-CoA from CO or CO2 + H2 Supports H2 as an electron donor with CO2.
  • carbon monoxide participates in Wood-Ljungdahl pathway biolink:participates_in

    CO can serve as a C1 input or intermediate for acetyl-CoA synthesis.

    • DOI:10.1016/j.bbapap.2008.08.012 acetyl-CoA from CO or CO2 + H2 Supports CO as substrate or intermediate.
  • Wood-Ljungdahl pathway has output acetyl-CoA RO:0002234

    Wood-Ljungdahl carbon fixation produces acetyl-CoA.

    • DOI:10.1016/j.tibtech.2019.05.008 reduced to one mol of acetyl-CoA Supports acetyl-CoA synthesis from CO2.
  • acetyl-CoA converted to acetate

    Acetyl-CoA is converted to acetate as the reduced product.

    • DOI:10.1016/j.tibtech.2019.05.008 further to acetate Supports acetate formation downstream of acetyl-CoA.
  • Homoacetogenesis produces acetate METPO:2007800

    Homoacetogenesis produces acetate as the sole reduced end product.

    • DOI:10.1023/A:1020514617738 reduce CO2 to acetate Supports acetate as the defining acetogenic product.
  • acetyl-CoA supports formation of ATP

    Conversion to acetate can conserve energy as ATP.

    • DOI:10.1016/j.tibtech.2019.05.008 further to acetate Review discusses acetate formation as the energy-conserving product branch.
  • carbon dioxide reduced by enzyme to formate

    CO2 is reduced to formate by formate dehydrogenase in the methyl branch.

    • DOI:10.1039/d4cb00099d CO2 to formate catalyzed by formate dehydrogenase (Fdh); core WLP methyl-branch step.
  • formate dehydrogenase catalyzes formate biolink:catalyzes

    Formate dehydrogenase produces formate from CO2.

    • DOI:10.1039/d4cb00099d CO2 -> formate catalyzed by formate dehydrogenase (Fdh).
  • formate converted by enzyme to formyl-tetrahydrofolate

    Formate is converted to formyl-THF by formyl-THF synthetase.

    • DOI:10.1039/d4cb00099d formate -> formyl-THF by formyl-THF synthetase (Fhs); methyl-branch step.
  • formyl-THF synthetase (Fhs) catalyzes formyl-tetrahydrofolate biolink:catalyzes

    Formyl-THF synthetase (Fhs) forms formyl-THF from formate.

    • DOI:10.1039/d4cb00099d formate -> formyl-THF by formyl-THF synthetase (Fhs).
  • methyl branch of WLP converges with carbonyl branch of WLP

    The methyl and carbonyl branches of the WLP converge at the ACS/CODH complex.

    • DOI:10.1186/s13068-024-02554-w eastern/methyl branch and carbonyl/western branch meet at the acetyl-CoA synthase/carbon monoxide dehydrogenase complex (ACS/CODH); canonical WLP architecture.
  • ACS/CODH complex produces acetyl-CoA METPO:2007800

    The ACS/CODH complex condenses the methyl and carbonyl groups into acetyl-CoA.

    • DOI:10.1186/s13068-024-02554-w the two WLP branches meet at the ACS/CODH complex to form acetyl-CoA.
  • acetate kinase generates ATP biolink:produces

    Acetate kinase generates ATP by substrate-level phosphorylation during acetate formation, the only WLP ATP-yielding step.

    • DOI:10.1039/d4cb00099d acetyl-CoA -> acetate via acetyl-phosphate with ATP from substrate-level phosphorylation (acetate kinase); WLP is otherwise net-zero ATP.
  • acetate kinase participates in substrate-level phosphorylation biolink:participates_in

    Acetate kinase mediates substrate-level phosphorylation in the acetate branch.

    • DOI:10.1039/d4cb00099d ATP from substrate-level phosphorylation at acetate kinase.
  • membrane energy-conservation module (Rnf/Ech) generates transmembrane ion gradient biolink:produces

    The membrane Rnf or Ech module translocates Na+/H+ to generate the transmembrane ion gradient.

    • DOI:10.1039/d4cb00099d Rnf transfers electrons from Fdred to NAD+ while translocating Na+/H+; Ech acts as Fd:H+ oxidoreductase.
    • DOI:10.3389/fmicb.2023.1185739 membrane-associated energy-conservation module involving Rnf or Ech plus ATP synthase.
  • transmembrane ion gradient drives ATP synthase

    The transmembrane ion gradient drives ATP synthase to conserve energy during acetogenesis.

    • DOI:10.3389/fmicb.2023.1185739 membrane-associated energy-conservation module ... plus ATP synthase.
  • ATP synthase produces ATP METPO:2007800

    ATP synthase produces ATP from the ion gradient, conserving energy in the near-thermodynamic-limit acetogenic metabolism.

    • DOI:10.3389/fmicb.2023.1185739 ATP synthase couples the ion gradient to ATP synthesis in acetogens.

Provenance

Source
METPO (2025-11-25)
Definition source
DOI:10.1016/j.tibtech.2019.05.008

Parent traits (1)

Synonyms (2)

  • Reductive acetyl-CoA pathway RELATED_SYNONYM · metpo.owl
  • Wood-Ljungdahl pathway RELATED_SYNONYM · metpo.owl

kg-microbe context

Matched 1 kg-microbe node via direct_metpo.

  • METPO:1000846 [-0.148, -0.934, -1.245, +0.063, …]

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).

Deep research

Generated by just research-trait; source: research/traits/metabolism/homoacetogenesis-deep-research-falcon.md

Unreviewed literature output — not curated TraitMech content Ontology identifiers suggested below have not been resolved against their ontologies, and some are known to be wrong. Check any CURIE against the source before using it.
# Homoacetogenesis (`METPO:1000846`): TraitMech curation report

## Executive curation recommendation

Homoacetogenesis should represent the **physiological capacity for reductive acetogenesis in which CO₂ is reduced through the Wood–Ljungdahl pathway (WLP) and acetate is the sole or principal reduced end product**. For autotrophic growth on H₂/CO₂, the canonical reaction is:

**2 CO₂ + 4 H₂ → CH₃COO⁻ + H⁺ + 2 H₂O**

A focused review reports ΔG°′ ≈ **−105 kJ mol⁻¹ acetate**, whereas under low-H₂ environmental conditions the available free energy may fall below approximately **−20 kJ mol⁻¹**, close to the energetic limit of microbial life. Thus, standard-state thermodynamics must not be interpreted as the energy actually available in situ. (karekar2022homoacetogenstheirmetabolism pages 1-3, baum2024theenergyconvertinghydrogenase pages 1-2)

The trait should **not** be assigned from an `acs`/`codh` gene, a partial WLP, acetate production, or even a complete WLP alone. Required evidence should ideally include growth or substrate-conversion experiments under anoxic conditions, CO₂ incorporation into acetate, and/or a mechanistically diagnostic perturbation. WLP enzymes also support assimilation, acetate oxidation, methanogenesis, and redox balancing in nonclassical organisms. (ragsdale2008enzymologyofthe pages 1-2, gencic2020diverseenergyconservingpathways pages 1-4, jiao2024cultivationofnovel pages 1-2)

## 1. Scope and boundaries

### Included phenotype

The core phenotype comprises:

1. anaerobic reduction of CO₂ through the reductive acetyl-CoA/Wood–Ljungdahl pathway;
2. convergence of a methyl branch and carbonyl branch at CODH/ACS;
3. production of acetyl-CoA and then acetate as the sole or predominant reduced product;
4. use of H₂, CO, formate, or substrate-derived reducing equivalents, depending on organism and growth condition;
5. bioenergetic coupling through a taxon-dependent Rnf- or Ech-type membrane system because the WLP-to-acetate sequence is substrate-level ATP-neutral. (basen2023editorialacetogens pages 1-2, karekar2022homoacetogenstheirmetabolism pages 1-3, baum2024theenergyconvertinghydrogenase pages 1-2)

Classical acetogens are strict anaerobic bacteria, but they are phylogenetically polyphyletic and occupy soils, sediments, extreme environments, and animal gastrointestinal tracts. The trait is therefore metabolic rather than taxonomic. (basen2023editorialacetogens pages 1-2, karekar2022homoacetogenstheirmetabolism pages 1-3, ragsdale2008enzymologyofthe pages 1-2)

### Boundary cases and exclusions

- **Broad “acetogenesis”:** acetate production by ordinary sugar fermentation is insufficient. Homoacetogenesis specifically requires reductive CO₂ incorporation through the WLP.
- **Assimilatory WLP:** methanogens, sulfate reducers, and other anaerobes can use WLP chemistry for cell-carbon synthesis without exhibiting the target phenotype. (ragsdale2008enzymologyofthe pages 1-2)
- **Reverse WLP/syntrophic acetate oxidation:** this consumes acetate and generates CO₂, the opposite trait direction. Acetate-utilizing methanogens can run relevant reactions in reverse. (ragsdale2008enzymologyofthe pages 1-2)
- **Methanogenesis:** hydrogenotrophic methanogens also consume H₂ and CO₂ but reduce carbon to methane rather than acetate. They commonly outcompete homoacetogens thermodynamically at low H₂, although environmental conditions such as high CO₂ can shift competition. (basen2023editorialacetogens pages 1-2, karekar2022homoacetogenstheirmetabolism pages 1-3)
- **Nonclassical WLP use:** in *Clostridioides difficile*, Δ`acsB`, enzyme assays, and product analyses showed that WLP flux disposes of carbohydrate-derived reducing equivalents and couples to butyrate formation; this is not automatically classical homoacetogenesis. (gencic2020diverseenergyconservingpathways pages 1-4)
- **Partial pathway or isolated modules:** 2024 comparative genomics found that Atribacterota lack a complete WLP even though some possess `acsABCDE`, hydrogenases, or reductive-glycine-pathway genes and produce acetate during fermentation. These observations do not establish homoacetogenesis. (jiao2024cultivationofnovel pages 1-2)

## 2. Candidate nodes grouped by type

Ontology identifiers below are deliberately conservative. Label-only nodes are preferable to uncertain or invented CURIEs.

### Trait and pathway nodes

| Candidate node | Suggested grounding | Curation comment |
|---|---|---|
| Homoacetogenesis | `METPO:1000846` | Quote verbatim in YAML. Reviewed class; parent supplied as `METPO:1000060`. |
| Wood–Ljungdahl pathway | Label; optionally map after pathway-database verification | Synonyms: reductive acetyl-CoA pathway, reductive acetyl-CoA pathway/WLP. |
| Methyl branch of WLP | Label-only | CO₂/formate to methyl-tetrahydrofolate and methyl-CoFeSP. |
| Carbonyl branch of WLP | Label-only | CO₂ to enzyme-bound CO. |
| Chemiosmotic energy conservation | `GO:0015988` candidate | Verify exact intended GO scope before committing. |
| ATP synthesis coupled to ion gradient | `GO:0015986` candidate | General process node; Na⁺ versus H⁺ is organism-specific. |

### Genes, proteins, enzymes, and complexes

| Node | Common gene labels | Suggested grounding/comment |
|---|---|---|
| Formate dehydrogenase / hydrogen-dependent CO₂ reductase | `fdh`, `fdhF`, `hdcr` subunits | Multiple non-orthologous systems; curate by species-specific complex rather than one universal gene. |
| Formate–tetrahydrofolate ligase | `fhs` | `EC:6.3.4.3` candidate. Consumes ATP during formate activation. |
| Methenyl-THF cyclohydrolase / methylene-THF dehydrogenase | often `folD` | Cofactor specificity and protein architecture vary. |
| Methylene-THF reductase | `metF`, frequently complex-associated | `EC:1.5.1.20` candidate; electron-bifurcating implementations are taxon-specific. |
| Methyltransferase | `acsE` | Transfers methyl group to corrinoid Fe–S protein. |
| Corrinoid iron–sulfur protein | `acsC`, `acsD` | Cobalamin-containing methyl carrier; subunit naming varies. |

Showing the first 60 of 225 lines of findings; the linked file also carries the run's front matter and the prompt it was given — read the full report.

Curation history

  1. · SEEDED_FROM_METPO · seed_from_metpo

    imported from data/raw/metpo.owl (CLASS)

  2. · ADDED_CAUSAL_GRAPH · codex

    Added DOI-backed causal graph for anaerobic Wood-Ljungdahl CO2 reduction, H2/CO inputs, acetyl-CoA formation, acetate product formation, and ATP conservation.

  3. · GROUND_CAUSAL_PREDICATES · claude

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

  4. · GROUND_CAUSAL_NODES · claude

    Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (ENVO:01001057×1, GO:0046358×1).

  5. · RENAME_PREDICATE_LABELS · claude

    Renamed 3 causal-edge predicate label(s) to align with existing groundings: input to → participates in ×2; occurs under → occurs in ×1.

  6. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (biolink:participates_in×2, biolink:occurs_in×1).

  7. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2007402×1).

  8. · FIX_NODE_GROUNDING_CURIE · claude

    Overwrote 1 causal-node grounding(s) to corrected CURIEs (phase-2 id-label fix; verified vs OAK).

  9. · FIX_NODE_GROUNDING_CURIE · claude

    Overwrote 1 causal-node grounding(s) (obsolete/wrong GO -> corrected, verified vs OAK).

  10. · ENRICH_CAUSAL_GRAPH · claude

    Added 11 evidence-backed generic edges (12 new nodes) from the deep-research report.

  11. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 7 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (biolink:catalyzes×2, METPO:2000202×2, biolink:produces×2, biolink:participates_in×1).

  12. · GROUND_CAUSAL_NODES · claude

    Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A081KVG3×1, UniProtKB:A0A415TT77×1).

  13. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A016XII7×1).

  14. · RETRACT_DEAD_UNIPROT_GROUNDINGS · claude

    Retracted 3 UniProtKB grounding(s) whose accessions are deleted from UniProt; nodes demoted to label-only pending re-grounding (docs/GROUNDING_POLICY.md)

  15. · GROUND_CAUSAL_NODES · claude

    Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0009326×1, GO:0008776×1).

  16. · MIGRATE_MICROBE_DOMAIN_EDGES · claude

    Re-grounded 1 causal edge(s) off microbe-domain METPO predicates (1 to has output), issue 301. The previous predicates are transitively rdfs:subPropertyOf METPO:2000001, whose rdfs:domain is METPO:1000525 (microbe), so a causal-graph subject entailed that the subject IS a microbe; CausalNodeTypeEnum has no organism member, so no such edge could ever satisfy the domain. Edge directions are unchanged - this pass only relabels and re-grounds. RO:0002234 (has output) is used where the subject is an activity, since biolink gives it the domain 'biological process or activity'; the METPO replacements are proposed in proposals/metpo_traitmech_v8 and v9 and are placeholder ids until METPO mints them.

  17. · MIGRATE_MICROBE_DOMAIN_EDGES_PART2 · claude

    Re-grounded 3 causal edge(s) off microbe-domain METPO predicates onto their causal-graph counterparts (3 to produces), issue 301 part 2. The previous predicates are transitively rdfs:subPropertyOf METPO:2000001, whose rdfs:domain is METPO:1000525 (microbe), so a causal-graph subject entailed that the subject IS a microbe; CausalNodeTypeEnum has no organism member, so no such edge could ever satisfy the domain. Each replacement is a 1:1 mirror of its source predicate that changes only the domain, so the claim each edge makes is unchanged and directions are unchanged. The replacements are proposed in proposals/metpo_traitmech_v9 and are placeholder ids until METPO mints them.