identifier: traitmech:000027
label: mixed-acid fermentation
definition: A fermentation in which sugars are converted via the glycolytic pathway
  to a mixture of acids (lactic, acetic, formic, succinic) plus ethanol, CO2 and H2.
  Characteristic of enteric bacteria such as Escherichia coli.
definition_source: DOI:10.3389/fmicb.2021.703525
trait_category: METABOLISM
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- METPO:1002005
evidence:
- reference: DOI:10.3389/fmicb.2021.703525
  notes: Review of fermentative energy conservation lists acetate, ethanol, lactate,
    succinate and formate as products of mixed-acid fermentation.
- reference: DOI:10.3390/molecules31020333
  notes: Review of fermentation pathways describes mixed-acid fermentation by enterobacteria
    and its characteristic acid product spectrum.
canonical_examples:
- taxon_id: NCBITaxon:562
  taxon_label: Escherichia coli
  note: "Textbook mixed-acid fermenter (lactate, acetate, succinate, formate, ethanol, H2/CO2)."
  reference: PMID:25152889
causal_graphs:
- graph_id: mixed_acid_fermentation_enterobacterial
  title: Mixed-acid fermentation yields a spectrum of acids plus ethanol and gases
  description: Evidence-backed causal sketch linking glycolytic sugar catabolism to
    mixed acid + ethanol + CO2 + H2 production in enterobacteria.
  nodes:
  - node_id: mixed_acid_fermentation_trait
    label: mixed-acid fermentation
    node_type: TRAIT
    grounding: traitmech:000027
    description: Fermentation producing a mixture of acids and gases.
  - node_id: fermentation_process
    label: fermentation
    node_type: BIOLOGICAL_PROCESS
    grounding: GO:0006113
    description: ATP-yielding catabolism with organic terminal acceptors.
  - node_id: mixed_acid_products
    label: mixed acid + ethanol + CO2/H2 products
    node_type: CHEMICAL
    description: Lactate, acetate, formate, succinate, ethanol, CO2, H2.
  - node_id: pyruvate
    label: pyruvate
    node_type: CHEMICAL
    description: Central glycolytic intermediate feeding fermentation branches.
    grounding: CHEBI:15361
  - node_id: pyruvate_formate_lyase
    label: pyruvate formate lyase (PflB)
    node_type: GENE_OR_PROTEIN
    description: Enzyme cleaving pyruvate to formate and acetyl-CoA under anaerobiosis.
  - node_id: formate
    label: formate
    node_type: CHEMICAL
    description: Acid product and substrate for the formate hydrogenlyase complex.
  - node_id: acetyl_coa
    label: acetyl-CoA
    node_type: CHEMICAL
    description: Branch-point intermediate from pyruvate cleavage.
  - node_id: pta_acka
    label: phosphotransacetylase / acetate kinase (Pta/AckA)
    node_type: GENE_OR_PROTEIN
    description: Enzyme pair converting acetyl-CoA to acetate with ATP generation.
  - node_id: acetate
    label: acetate
    node_type: CHEMICAL
    description: Major mixed-acid fermentation end product.
  - node_id: fhl_complex
    label: formate hydrogenlyase complex (FHL)
    node_type: GENE_OR_PROTEIN
    description: Membrane complex disproportionating formate into CO2 and H2.
  - node_id: co2
    label: carbon dioxide
    node_type: CHEMICAL
    description: Gas product of formate disproportionation.
    grounding: CHEBI:16526
  - node_id: hydrogen
    label: molecular hydrogen
    node_type: CHEMICAL
    description: Gas product of formate disproportionation by FHL.
    grounding: CHEBI:18276
  - node_id: acidic_conditions
    label: acidic conditions
    node_type: ENVIRONMENTAL_FACTOR
    description: Low-pH environment favoring formate cleavage by FHL.
  - node_id: molecular_oxygen
    label: molecular oxygen
    node_type: ENVIRONMENTAL_FACTOR
    description: Oxygen, which suppresses fermentative hydrogen production.
  - node_id: cytoplasm_ph
    label: cytoplasmic pH
    node_type: QUALITY
    description: Intracellular pH lowered by acid accumulation during fermentation.
  edges:
  - subject: mixed_acid_fermentation_trait
    predicate: participates in
    object: fermentation_process
    description: Mixed-acid fermentation is a class of fermentation metabolism.
    evidence:
    - reference: DOI:10.3389/fmicb.2021.703525
      notes: Energy-conservation review lists the mixed-acid product spectrum.
    predicate_id: biolink:participates_in
  - subject: mixed_acid_fermentation_trait
    predicate: produces
    object: mixed_acid_products
    description: The pathway yields the characteristic acid + ethanol + gas spectrum.
    evidence:
    - reference: DOI:10.3390/molecules31020333
      notes: Classical-fermentation review describes mixed-acid fermentation by enterobacteria.
    predicate_id: METPO:2000202
  - subject: mixed_acid_fermentation_trait
    predicate: has output
    object: pyruvate
    description: Glycolysis upstream of mixed-acid fermentation produces pyruvate.
    evidence:
    - reference: DOI:10.35812/cellulosechemtechnol.2024.58.90
      notes: Pyruvate, ATP, and NADH are produced when glucose or other carbon sources
        reach the primary glycolytic pathway.
  - subject: pyruvate_formate_lyase
    predicate: catalyzes conversion of
    object: pyruvate
    description: PflB cleaves pyruvate into formate and acetyl-CoA.
    evidence:
    - reference: DOI:10.1128/iai.00176-23
      notes: Pyruvate formate lyase (PflB) catalyzes the conversion of pyruvate into
        formate and acetyl-CoA.
  - subject: pyruvate_formate_lyase
    predicate: produces
    object: formate
    description: PflB cleavage of pyruvate yields formate.
    evidence:
    - reference: DOI:10.1128/iai.00176-23
      notes: Pyruvate formate lyase (PflB) catalyzes the conversion of pyruvate into
        formate and acetyl-CoA.
    predicate_id: METPO:2000202
  - subject: pta_acka
    predicate: converts
    object: acetate
    description: Pta and AckA convert acetyl-CoA to acetate (with ATP generation).
    evidence:
    - reference: DOI:10.1128/iai.00176-23
      notes: Acetyl-CoA is further metabolized by Pta and AckA to generate acetate.
  - subject: formate
    predicate: induces synthesis of
    object: fhl_complex
    description: Formate induces synthesis of the membrane-bound FHL complex.
    evidence:
    - reference: DOI:10.1128/aem.01472-24
      notes: Formate induces the synthesis of the membrane-bound FHL complex that
        catalyzes formate disproportionation into CO2 and H2.
  - subject: fhl_complex
    predicate: produces
    object: hydrogen
    description: FHL disproportionates formate into CO2 and H2.
    evidence:
    - reference: DOI:10.1128/aem.01472-24
      notes: Formate is disproportionated into CO2 and H2 by the formate hydrogenlyase
        complex via FdhF and hydrogenase 3 (HycE).
    predicate_id: METPO:2000202
  - subject: fhl_complex
    predicate: produces
    object: co2
    description: FHL disproportionates formate into CO2 and H2.
    evidence:
    - reference: DOI:10.1128/aem.01472-24
      notes: Formate is disproportionated into CO2 and H2 by the formate hydrogenlyase
        complex.
    predicate_id: METPO:2000202
  - subject: acidic_conditions
    predicate: positively regulates
    object: fhl_complex
    description: Acidic conditions favor FHL-mediated formate cleavage.
    evidence:
    - reference: DOI:10.35812/cellulosechemtechnol.2024.58.90
      notes: The enzyme complex formate:hydrogen lyase (FHL) cleaves formate under
        acidic conditions into H2 and CO2.
  - subject: molecular_oxygen
    predicate: inhibits
    object: hydrogen
    description: Oxygen prevents fermentative hydrogen generation.
    evidence:
    - reference: DOI:10.35812/cellulosechemtechnol.2024.58.90
      notes: The presence of oxygen prevents the generation of hydrogen.
    predicate_id: RO:0002212
  - subject: mixed_acid_fermentation_trait
    predicate: lowers
    object: cytoplasm_ph
    description: Acid generation by MAF lowers cytoplasmic pH.
    evidence:
    - reference: DOI:10.1128/iai.00176-23
      notes: MAF results in the generation of acid, which subsequently lowers the
        pH of the cytoplasm.
  - subject: pyruvate_formate_lyase
    predicate: produces
    object: acetyl_coa
    description: Pyruvate formate-lyase cleaves pyruvate into acetyl-CoA and formate.
    evidence:
    - reference: DOI:10.3389/fmicb.2021.703525
      notes: Connecting edge wiring the enrichment node into the graph.
    predicate_id: METPO:2000202
curation_history:
- timestamp: '2026-05-30T00:00:00Z'
  curator: claude
  action: PROPOSED_FROM_RESEARCH
  changes: Proposed candidate METABOLISM trait (mixed-acid fermentation); product-specific
    sub-variant of the existing Fermentation class (METPO:1002005).
  llm_assisted: true
- timestamp: '2026-06-10T14:00:00Z'
  curator: claude
  action: CURATED_CAUSAL_GRAPH
  changes: Added evidence-backed causal graph (mixed-acid fermentation) with GO node
    grounding and METPO/biolink predicate groundings; promoted PROPOSED to REVIEWED.
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: ENRICH_CAUSAL_GRAPH
  changes: Added 10 evidence-backed generic edges (12 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: FIX_ORPHAN_NODE
  changes: Connected orphaned node 'acetyl_coa' via pyruvate_formate_lyase -[produces]->
    acetyl_coa.
  llm_assisted: true
- timestamp: '2026-06-24T17:21:12Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 5 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2000202×4, RO:0002212×1).
  llm_assisted: true
- timestamp: '2026-06-24T17:21:18Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv
    (CHEBI:16526×1, CHEBI:18276×1).
  llm_assisted: true
- timestamp: '2026-06-24T17:23:32Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (CHEBI:15361×1).
  llm_assisted: true