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
Edge evidence
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Homoacetogenesis
occurs in
anaerobic condition
biolink:occurs_inHomoacetogenesis is an anaerobic acetogenic metabolism.
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DOI:10.1023/A:1020514617738obligately anaerobic bacteria
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Homoacetogenesis
has mechanistic pathway
Wood-Ljungdahl pathway
Homoacetogenesis proceeds through the Wood-Ljungdahl pathway.
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DOI:10.1016/j.tibtech.2019.05.008Wood-Ljungdahl pathway
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carbon dioxide
participates in
Wood-Ljungdahl pathway
biolink:participates_inCO2 is reduced through the Wood-Ljungdahl pathway.
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DOI:10.1016/j.tibtech.2019.05.008carbon dioxide are reduced
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molecular hydrogen
provides electrons for
Wood-Ljungdahl pathway
METPO:2007402Hydrogen can provide reducing equivalents for CO2 reduction.
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DOI:10.1016/j.bbapap.2008.08.012acetyl-CoA from CO or CO2 + H2
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carbon monoxide
participates in
Wood-Ljungdahl pathway
biolink:participates_inCO can serve as a C1 input or intermediate for acetyl-CoA synthesis.
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DOI:10.1016/j.bbapap.2008.08.012acetyl-CoA from CO or CO2 + H2
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Wood-Ljungdahl pathway
has output
acetyl-CoA
RO:0002234Wood-Ljungdahl carbon fixation produces acetyl-CoA.
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DOI:10.1016/j.tibtech.2019.05.008reduced to one mol of acetyl-CoA
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acetyl-CoA
converted to
acetate
Acetyl-CoA is converted to acetate as the reduced product.
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DOI:10.1016/j.tibtech.2019.05.008further to acetate
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Homoacetogenesis
produces
acetate
METPO:2007800Homoacetogenesis produces acetate as the sole reduced end product.
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DOI:10.1023/A:1020514617738reduce CO2 to acetate
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acetyl-CoA
supports formation of
ATP
Conversion to acetate can conserve energy as ATP.
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DOI:10.1016/j.tibtech.2019.05.008further to acetate
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carbon dioxide
reduced by enzyme to
formate
CO2 is reduced to formate by formate dehydrogenase in the methyl branch.
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DOI:10.1039/d4cb00099d
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formate dehydrogenase
catalyzes
formate
biolink:catalyzesFormate dehydrogenase produces formate from CO2.
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DOI:10.1039/d4cb00099d
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formate
converted by enzyme to
formyl-tetrahydrofolate
Formate is converted to formyl-THF by formyl-THF synthetase.
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DOI:10.1039/d4cb00099d
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formyl-THF synthetase (Fhs)
catalyzes
formyl-tetrahydrofolate
biolink:catalyzesFormyl-THF synthetase (Fhs) forms formyl-THF from formate.
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DOI:10.1039/d4cb00099d
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methyl branch of WLP
converges with
carbonyl branch of WLP
The methyl and carbonyl branches of the WLP converge at the ACS/CODH complex.
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DOI:10.1186/s13068-024-02554-w
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ACS/CODH complex
produces
acetyl-CoA
METPO:2007800The ACS/CODH complex condenses the methyl and carbonyl groups into acetyl-CoA.
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DOI:10.1186/s13068-024-02554-w
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acetate kinase
generates
ATP
biolink:producesAcetate kinase generates ATP by substrate-level phosphorylation during acetate formation, the only WLP ATP-yielding step.
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DOI:10.1039/d4cb00099d
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acetate kinase
participates in
substrate-level phosphorylation
biolink:participates_inAcetate kinase mediates substrate-level phosphorylation in the acetate branch.
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DOI:10.1039/d4cb00099d
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membrane energy-conservation module (Rnf/Ech)
generates
transmembrane ion gradient
biolink:producesThe membrane Rnf or Ech module translocates Na+/H+ to generate the transmembrane ion gradient.
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DOI:10.1039/d4cb00099d -
DOI:10.3389/fmicb.2023.1185739
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transmembrane ion gradient
drives
ATP synthase
The transmembrane ion gradient drives ATP synthase to conserve energy during acetogenesis.
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DOI:10.3389/fmicb.2023.1185739
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ATP synthase
produces
ATP
METPO:2007800ATP synthase produces ATP from the ion gradient, conserving energy in the near-thermodynamic-limit acetogenic metabolism.
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DOI:10.3389/fmicb.2023.1185739
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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
- Wood-Ljungdahl pathway
kg-microbe context
Matched 1 kg-microbe node via direct_metpo.
METPO:1000846[-0.148, -0.934, -1.245, +0.063, …]
Nearest neighbors in embedding space
- metabolism Oxidative phosphorylation 0.971
- metabolism Substrate-level phosphorylation 0.971
- metabolism Syntrophy 0.971
- metabolism Disproportionation 0.970
- metabolism Cable bacteria metabolism 0.968
- metabolism Electron transfer 0.963
- metabolism starch degradation 0.939
- metabolism 3-hydroxypropionate bicycle 0.939
Deep research
# 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. |
Curation history
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SEEDED_FROM_METPO · seed_from_metpo
imported from data/raw/metpo.owl (CLASS)
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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.
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GROUND_CAUSAL_PREDICATES · claude
Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2000202×2).
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GROUND_CAUSAL_NODES · claude
Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (ENVO:01001057×1, GO:0046358×1).
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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.
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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).
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GROUND_CAUSAL_PREDICATES · claude
Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2007402×1).
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FIX_NODE_GROUNDING_CURIE · claude
Overwrote 1 causal-node grounding(s) to corrected CURIEs (phase-2 id-label fix; verified vs OAK).
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FIX_NODE_GROUNDING_CURIE · claude
Overwrote 1 causal-node grounding(s) (obsolete/wrong GO -> corrected, verified vs OAK).
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ENRICH_CAUSAL_GRAPH · claude
Added 11 evidence-backed generic edges (12 new nodes) from the deep-research report.
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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).
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GROUND_CAUSAL_NODES · claude
Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A081KVG3×1, UniProtKB:A0A415TT77×1).
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GROUND_CAUSAL_NODES · claude
Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A016XII7×1).
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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)
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GROUND_CAUSAL_NODES · claude
Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0009326×1, GO:0008776×1).
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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.
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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.