TraitMech

TraitMech › METABOLISM

Acetogenesis

METPO:1000845 · CLASS · REVIEWED

A metabolism that produces acetate as the primary end product through the reduction of carbon dioxide or other carbon compounds using the Wood-Ljungdahl pathway, typically performed by acetogenic bacteria under anaerobic conditions.

Acetogenesis Wood-Ljungdahl mechanism

Evidence-backed causal sketch linking anaerobic carbon fixation through the Wood-Ljungdahl pathway to acetate production.

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

Edge evidence

  • Acetogenesis occurs in anaerobic condition biolink:occurs_in

    Acetogenesis is typically an anaerobic metabolism.

    • DOI:10.1016/j.bbapap.2008.08.012 grow organisms and work with enzymes under strictly oxygen-free conditions Review emphasizes oxygen-free handling for acetogenic enzymes and organisms.
  • Acetogenesis has mechanistic pathway Wood-Ljungdahl pathway

    The Wood-Ljungdahl pathway is the central acetogenic carbon-fixation route.

    • DOI:10.1016/j.bbapap.2008.08.012 Wood-Ljungdahl Pathway of CO2 Fixation Review title and scope support pathway assignment.
  • carbon dioxide participates in Wood-Ljungdahl pathway biolink:participates_in

    Carbon dioxide is fixed through the Wood-Ljungdahl pathway.

    • DOI:10.1016/j.bbapap.2008.08.012 CO2 Fixation Supports CO2 as a pathway substrate.
  • carbon monoxide participates in Wood-Ljungdahl pathway biolink:participates_in

    Carbon monoxide can be converted through the acetogenic pathway.

    • DOI:10.1196/annals.1419.015 convert carbon dioxide and CO into acetyl-CoA Supports CO as a substrate for acetogenic acetyl-CoA synthesis.
  • Wood-Ljungdahl pathway has output acetyl-CoA RO:0002234

    The Wood-Ljungdahl pathway synthesizes acetyl-CoA.

    • DOI:10.1196/annals.1419.015 convert carbon dioxide and CO into acetyl-CoA Supports acetyl-CoA as pathway product.
  • acetyl-CoA precursor of acetate

    Acetyl-CoA is converted onward to acetate in acetogenesis.

    • DOI:10.1016/j.bbapap.2008.08.012 Energy metabolism associated with acetogenesis Review discusses acetogenic energy metabolism downstream of acetyl-CoA synthesis.
  • carbon dioxide is converted to formate

    CO2 is reduced to formate by formate dehydrogenase / HDCR, the first methyl-branch step.

    • DOI:10.3389/fbioe.2024.1395540 FDH reduces CO2 to formate; HDCR catalyzes hydrogen-dependent CO2 reduction to formate (methyl-branch core step).
  • formate is converted to 10-formyl-tetrahydrofolate

    Formate is condensed onto tetrahydrofolate by formyl-THF synthetase (Fhs).

    • DOI:10.3389/fbioe.2024.1395540 FTS (formyl-THF synthetase) converts formate to formyl-THF consuming 1 ATP; canonical WLP methyl-branch step.
  • 10-formyl-tetrahydrofolate is converted to 5,10-methylene-tetrahydrofolate

    Formyl-THF is processed by cyclohydrolase and methylene-THF dehydrogenase (FolD) to methylene-THF.

    • DOI:10.34726/hss.2024.114566 5,10-methenyl-THF cyclohydrolase and NAD-dependent 5,10-methylene-THF dehydrogenase convert formyl-THF to methylene-THF.
  • 5,10-methylene-tetrahydrofolate is converted to 5-methyl-tetrahydrofolate

    Methylene-THF is reduced to methyl-THF by methylene-THF reductase (MTHFR).

    • DOI:10.3389/fbioe.2024.1395540 MTHFR reduces methenyl-THF to methylene-THF to methyl-THF; common acetogen methyl-branch step.
  • carbon dioxide is converted to carbon monoxide

    CO2 is reduced to CO by carbon monoxide dehydrogenase (CODH) in the carbonyl branch.

    • DOI:10.34726/hss.2024.114566 In the carbonyl branch CODH reduces CO2 to CO; central carbonyl-branch step.
  • acetyl-CoA is converted to acetyl phosphate

    Acetyl-CoA is converted to acetyl phosphate by phosphotransacetylase (PTA).

    • DOI:10.3389/fbioe.2024.1395540 PTA and ACK convert acetyl-CoA to acetate; PTA yields acetyl phosphate.
  • acetyl phosphate is converted to acetate

    Acetyl phosphate is converted to acetate by acetate kinase (ACK), yielding ATP by substrate-level phosphorylation.

    • DOI:10.3389/fbioe.2024.1395540 ACK (acetate kinase) converts acetyl-phosphate to acetate, yielding ATP via SLP; trait-defining end-product step.
  • acetate kinase step has input acetyl phosphate RO:0002233

    Acetate kinase consumes acetyl phosphate in the substrate-level phosphorylation step.

    • DOI:10.3389/fbioe.2024.1395540 ACK convert acetyl-phosphate to acetate, yielding ATP via SLP.
  • acetate kinase step has output ATP RO:0002234

    The acetate kinase step generates ATP via substrate-level phosphorylation.

    • DOI:10.3389/fbioe.2024.1395540 ACK convert acetyl-phosphate to acetate, yielding ATP via SLP.

Provenance

Source
METPO (2025-11-25)
Author
Jed Dongjin Kim-Ozaeta
Definition source
DOI:10.1016/j.bbapap.2008.08.012

Parent traits (1)

Synonyms (1)

  • Acetate fermentation RELATED_SYNONYM · metpo.owl

kg-microbe context

Matched 1 kg-microbe node via direct_metpo.

  • METPO:1000845 [-0.195, -1.369, -0.856, +1.197, …]

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/acetogenesis-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. 
# TraitMech Curation Report: Acetogenesis

## 1. Curation target and scope

- **Trait:** Acetogenesis
- **Trait identifier:** **METPO:1000845**
- **Category / kind / status:** METABOLISM / CLASS / REVIEWED
- **Parent:** METPO:1000060
- **Recommended operational definition:** an anaerobic physiological capacity in which the Wood–Ljungdahl pathway (WLP; reductive acetyl-CoA pathway) functions in carbon assimilation and redox/energy conservation, producing acetyl-CoA from C1 carbon and normally disposing of that acetyl-CoA principally as acetate.

Two CO₂ molecules supply the methyl and carbonyl carbons of acetyl-CoA. In the methyl branch, CO₂ is reduced through formate and tetrahydrofolate-bound intermediates to methyl-THF. In the carbonyl branch, CO₂ is reduced to CO, or exogenous CO is used directly. CODH/ACS joins the methyl group, CO, and CoA to form acetyl-CoA; conversion through acetyl phosphate to acetate produces ATP by substrate-level phosphorylation. Acetogens also require chemiosmotic energy conservation because ATP consumption in the methyl branch leaves the core substrate-level pathway near net-zero ATP. Rnf- or Ech-generated ion gradients drive ATP synthase. A recent review estimates approximately **0.3 mol ATP per mol acetate** for Na⁺-dependent *Acetobacterium woodii* growing with H₂/CO₂. (bae2024harnessingacetogenicbacteria pages 2-3)

### Inclusion criteria

A strain or community should be assigned **METPO:1000845** when evidence shows:

1. operation of the WLP in the reductive direction;
2. acetyl-CoA synthesis from CO₂, CO, formate, methanol-derived C1 units, or fermentatively generated reducing equivalents;
3. acetate as the primary or characteristic reduced end product; and
4. preferably, physiological evidence such as growth, isotope incorporation, stoichiometric acetate production, transcript/protein expression, or flux through both WLP branches.

The WLP is a defining feature because it can serve simultaneously in acetyl-CoA synthesis, terminal electron acceptance, energy conservation, and carbon fixation. Approximately 200 genes may support autotrophy even though the core WLP genes occupy a much smaller locus; therefore, trait inference should not be based on one marker alone. (fackler2021steppingonthe pages 1-5)

### Boundary cases

- **Ordinary acetate fermentation is not automatically acetogenesis.** Glycolytic or amino-acid fermentation may produce acetate through acetyl-CoA without reductive WLP operation. “Acetate fermentation,” although listed as a synonym, is consequently too broad for automated inference.
- **Acetogenic bacteria need not be taxonomically monophyletic.** The phenotype is metabolic, not a clade designation. More than 100 acetogenic species have been described from soils, sediments, sludge, and intestinal systems. (bae2024harnessingacetogenicbacteria pages 2-3)
- **WLP presence is not sufficient.** Methanogens use related acetyl-CoA pathway modules, and some organisms use the pathway for assimilation without acetate being the principal end product.
- **Reverse WLP is not acetogenesis.** Syntrophic acetate oxidation consumes acetate and runs the pathway in the oxidative direction.
- **CODH alone is insufficient.** In a 2024 human-gut survey, over 1,000 representative genomes encoded putative nickel CODH, but **79%** of WLP-like gene sets lacked the formate-producing step. Such genomes may use CO for biosynthesis or possess a degenerate, heterotrophic WLP rather than perform canonical autotrophic acetogenesis. (katayama2024phylogeneticdiversityofa pages 1-7, katayama2024phylogeneticdiversityof pages 16-16)
- **Non-acetate products require phenotype-level qualification.** *Clostridium autoethanogenum* can produce ethanol and other products from gases. Such strains retain acetogenic metabolism, but a condition in which ethanol or an engineered chemical dominates should not be represented as “acetate is the primary product” without measurements. (bae2024harnessingacetogenicbacteria pages 2-3, davin2024clostridiumautoethanogenumalters pages 1-2)

## 2. Candidate causal-graph nodes

Identifiers below are conservative suggestions. Labels without a verified stable identifier should remain label-only rather than receive an inferred CURIE.

### Trait and pathway nodes

| Candidate node | Suggested grounding | Curation note |
|---|---|---|
| Acetogenesis | **METPO:1000845** | Target trait; preserve CURIE verbatim. |
| Wood–Ljungdahl pathway | MetaCyc:CODH-PWY; KEGG module candidate M00377 | Verify database-version semantics before committing; pathway may occur outside acetogenic phenotypes. |
| Methyl branch of WLP | Label-only candidate | CO₂/formate to methyl-THF. |
| Carbonyl branch of WLP | Label-only candidate | CO₂ to CO, or direct exogenous CO utilization. |
| Substrate-level phosphorylation during acetate formation | GO:0006084 is acetate metabolism, but not an exact representation | Prefer a process label plus explicit reaction edges. |
| Chemiosmotic energy conservation | GO:0015986 is ATP synthesis coupled proton transport | Na⁺-coupled systems require more precise representation. |

### Chemicals and cofactors

| Node | Suggested CURIE |
|---|---|
| carbon dioxide | CHEBI:16526 |
| carbon monoxide | CHEBI:17245 |
| dihydrogen | CHEBI:18276 |
| formate | CHEBI:15740 |
| acetate | CHEBI:30089 |
| acetyl-CoA | CHEBI:15351 |
| coenzyme A | CHEBI:15346 |
| ATP | CHEBI:15422 |
| ADP | CHEBI:16761 |

Showing the first 60 of 220 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 carbon fixation and acetate production.

  3. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2000202×1).

  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. · FIX_NODE_GROUNDING_CURIE · claude

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

  8. · FIX_NODE_GROUNDING_CURIE · claude

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

  9. · REMOVE_REDUNDANT_SYNONYM · claude

    Removed 1 synonym(s) whose text duplicated the label (seeder redundancy; no information lost).

  10. · ENRICH_CAUSAL_GRAPH · claude

    Added 8 evidence-backed generic edges (6 new nodes) from the deep-research report.

  11. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2000202×1).

  12. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:15350×1).

  13. · 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.

  14. · MIGRATE_MICROBE_DOMAIN_EDGES_PART2 · claude

    Re-grounded 1 causal edge(s) off microbe-domain METPO predicates onto their causal-graph counterparts (1 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.

  15. · ENRICH_CAUSAL_GRAPH · claude

    Modelled the acetate kinase step as an explicit BIOLOGICAL_PROCESS node and split `acetyl_phosphate produces atp` into `acetate_kinase_step has input acetyl_phosphate` (RO:0002233) and `acetate_kinase_step has output atp` (RO:0002234), issue 331. The old edge had a CHEMICAL subject on METPO:2007800, whose definition is that the activity or state of the subject brings the object into existence - a chemical has neither in that sense. RO:0001001 (derives into) did not fit either, because ATP's matter comes mostly from ADP and only the phosphoryl group transfers, failing that relation's inherits-the-significant-portion-of-the-matter test. The process the edge description already named was simply not in the graph; both new edges are range-correct and the step is wired on both sides so nothing is orphaned. This was the last CHEMICAL-subject produces edge, which let METPO:2007800's subject_types gate drop CHEMICAL. Two modelling choices are recorded here as decisions rather than left as omissions (issue 331 review). The node is typed BIOLOGICAL_PROCESS rather than MOLECULAR_FUNCTION, which would have grounded to GO:0008776 (acetate kinase activity) via mappings/node_grounding.tsv - this trait's own research report asks for a process label plus explicit reaction edges for the substrate-level phosphorylation step, and that is what this is. And the step carries has-output atp but deliberately not has-output acetate, because the existing acetyl_phosphate is-converted-to acetate edge already states that half of the reaction on the chemical chain; asserting it again at the process level is the duplication at two levels of description that issue 303 criticised in dissimilatory_iron_reduction.