identifier: METPO:1000651
label: methylotrophic
definition: A trophic type in which an organism obtains energy and carbon from reduced
  one-carbon compounds.
definition_source: DOI:10.3389/fbioe.2021.787791
trait_category: PHYSIOLOGY
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- METPO:1000631
synonyms:
- synonym_text: TT_methylotroph
  synonym_type: RELATED_SYNONYM
  source: metpo.owl
- synonym_text: methylotroph
  synonym_type: RELATED_SYNONYM
  source: metpo.owl
- synonym_text: methylotrophy
  synonym_type: RELATED_SYNONYM
  source: metpo.owl
evidence:
- reference: DOI:10.3389/fbioe.2021.787791
  snippet: methanol utilization in methylotrophy
  notes: Review supports methanol oxidation and formaldehyde assimilation as central
    methylotrophy mechanisms.
canonical_examples:
- taxon_id: NCBITaxon:408
  taxon_label: Methylorubrum extorquens
  note: "Model facultative methylotroph (formerly Methylobacterium extorquens; strain AM1)."
  reference: PMID:12730156
causal_graphs:
- graph_id: methylotrophic_methanol_assimilation
  title: Methanol-based methylotrophy mechanism
  description: DOI-backed graph for methanol oxidation to formaldehyde and assimilation
    through native methylotrophy pathways.
  nodes:
  - node_id: methylotrophic_trait
    label: methylotrophic
    node_type: TRAIT
    grounding: METPO:1000651
    description: Trophic type using reduced one-carbon compounds for carbon and energy.
  - node_id: methanol
    label: methanol
    node_type: CHEMICAL
    grounding: CHEBI:17790
    description: Reduced C1 substrate used by many methylotrophs.
  - node_id: methanol_dehydrogenase
    label: methanol dehydrogenase
    node_type: GENE_OR_PROTEIN
    description: Primary enzyme oxidizing methanol in methylotrophy.
    grounding: UniProtKB:A0A010SCY7
  - node_id: pqq_dependent_mdh
    label: PQQ-dependent methanol dehydrogenase
    node_type: GENE_OR_PROTEIN
    description: Periplasmic methanol dehydrogenase class in Gram-negative methylotrophs.
    grounding: UniProtKB:A0A4U8YZA6
  - node_id: periplasmic_space
    label: periplasmic space
    node_type: CELLULAR_LOCALIZATION
    description: Cellular compartment where PQQ-dependent MDH oxidizes methanol in
      Gram-negative methylotrophs.
    grounding: GO:0042597
  - node_id: formaldehyde
    label: formaldehyde
    node_type: CHEMICAL
    grounding: CHEBI:16842
    description: Central intermediate produced by methanol oxidation.
  - node_id: rump_cycle
    label: ribulose monophosphate cycle
    node_type: PATHWAY
    description: Prokaryotic formaldehyde assimilation pathway.
    grounding: GO:0019647
  - node_id: serine_pathway
    label: serine pathway
    node_type: PATHWAY
    description: Prokaryotic formaldehyde assimilation pathway.
  - node_id: biomass_precursor
    label: biomass precursor
    node_type: BIOLOGICAL_PROCESS
    description: Assimilated cellular carbon derived from formaldehyde.
  - node_id: hexulose_phosphate_synthase
    label: 3-hexulose-6-phosphate synthase (Hps)
    node_type: GENE_OR_PROTEIN
    description: Hallmark RuMP-cycle enzyme that condenses formaldehyde for assimilation.
  - node_id: serine_glyoxylate_aminotransferase
    label: serine-glyoxylate aminotransferase (SgaA/SGT)
    node_type: GENE_OR_PROTEIN
    description: Conserved serine-cycle enzyme found across methylotroph genomes.
  - node_id: hydroxypyruvate_reductase
    label: hydroxypyruvate reductase (HprA/HPR)
    node_type: GENE_OR_PROTEIN
    description: Ubiquitous serine-cycle enzyme reducing hydroxypyruvate.
  - node_id: formaldehyde_dehydrogenase
    label: formaldehyde dehydrogenase (Fld/FDH)
    node_type: GENE_OR_PROTEIN
    description: Enzyme oxidizing formaldehyde to formate during dissimilation.
  - node_id: formate
    label: formate
    node_type: CHEMICAL
    description: C1 intermediate produced by formaldehyde oxidation.
  - node_id: formate_dehydrogenase
    label: formate dehydrogenase (Fdh)
    node_type: GENE_OR_PROTEIN
    description: Enzyme oxidizing formate to CO2 in the dissimilatory branch.
  - node_id: carbon_dioxide
    label: carbon dioxide
    node_type: CHEMICAL
    description: Terminal product of C1 dissimilatory oxidation.
    grounding: CHEBI:16526
  - node_id: mxa_methanol_dehydrogenase
    label: MxaFI methanol dehydrogenase
    node_type: GENE_OR_PROTEIN
    description: Calcium-dependent methanol dehydrogenase of the PQQ alcohol dehydrogenase
      family.
  - node_id: pqq
    label: pyrroloquinoline quinone (PQQ)
    node_type: CHEMICAL
    description: Redox cofactor required by methanol dehydrogenases.
  - node_id: calcium_ion
    label: calcium ion (Ca2+)
    node_type: CHEMICAL
    description: Active-site metal cofactor of MxaFI-type methanol dehydrogenase.
  edges:
  - subject: methylotrophic_trait
    predicate: uses substrate
    object: methanol
    description: Methanol is a representative reduced C1 substrate for methylotrophy.
    evidence:
    - reference: DOI:10.3389/fbioe.2021.787791
      snippet: methanol utilization in methylotrophy
      notes: Supports methanol as a methylotrophic substrate; other C1 substrates
        are not modeled here.
  - subject: methanol_dehydrogenase
    predicate: oxidizes
    object: methanol
    description: Methanol dehydrogenase catalyzes the first methanol oxidation step.
    evidence:
    - reference: DOI:10.3389/fbioe.2021.787791
      snippet: Mdh is a primary enzyme
      notes: Supports methanol dehydrogenase as the primary methanol-utilization enzyme.
    predicate_id: METPO:2000016
  - subject: methanol
    predicate: oxidized to
    object: formaldehyde
    description: Methanol oxidation produces formaldehyde for assimilation or further
      oxidation.
    evidence:
    - reference: DOI:10.3389/fbioe.2021.787791
      snippet: converts methanol to formaldehyde
      notes: Supports methanol-to-formaldehyde conversion.
    predicate_id: METPO:2007405
  - subject: pqq_dependent_mdh
    predicate: located in
    object: periplasmic_space
    description: PQQ-dependent MDH oxidizes methanol in the periplasm of Gram-negative
      methylotrophs.
    evidence:
    - reference: DOI:10.3389/fbioe.2021.787791
      snippet: oxidation of methanol occurs in the periplasmic space
      notes: Supports periplasmic localization of PQQ-dependent methanol oxidation.
    predicate_id: biolink:located_in
  - subject: pqq_dependent_mdh
    predicate: produces
    object: formaldehyde
    description: PQQ-dependent methanol dehydrogenase produces formaldehyde from methanol.
    evidence:
    - reference: DOI:10.3389/fbioe.2021.787791
      snippet: converts methanol to formaldehyde
      notes: Source supports formaldehyde as the product of methanol oxidation by
        methanol dehydrogenases.
    predicate_id: METPO:2000202
  - subject: formaldehyde
    predicate: assimilated by
    object: rump_cycle
    description: Formaldehyde can enter the RuMP cycle for growth on methanol.
    evidence:
    - reference: DOI:10.3389/fbioe.2021.787791
      snippet: ribulose monophosphate (RuMP) cycle
      notes: Supports RuMP as a native formaldehyde assimilation pathway.
  - subject: formaldehyde
    predicate: assimilated by
    object: serine_pathway
    description: Formaldehyde can enter the serine pathway for growth on methanol.
    evidence:
    - reference: DOI:10.3389/fbioe.2021.787791
      snippet: serine pathway
      notes: Supports the serine pathway as a native formaldehyde assimilation route.
  - subject: rump_cycle
    predicate: produces
    object: biomass_precursor
    description: RuMP assimilation incorporates C1 carbon into cellular material.
    evidence:
    - reference: DOI:10.3389/fbioe.2021.787791
      snippet: growth support of microorganisms in methanol
      notes: Supports assimilation pathways as growth-supporting routes.
    predicate_id: METPO:2000202
  - subject: hexulose_phosphate_synthase
    predicate: catalyzes
    object: rump_cycle
    description: Hps drives formaldehyde assimilation in the RuMP cycle.
    evidence:
    - reference: DOI:10.1038/s41467-023-43610-7
      notes: The RuMP pathway relies on 3-hexulose 6-phosphate synthase (Hps) and
        phosphohexose isomerase (Phi) to assimilate formaldehyde.
    predicate_id: biolink:catalyzes
  - subject: serine_glyoxylate_aminotransferase
    predicate: catalyzes
    object: serine_pathway
    description: SgaA/SGT is a conserved serine-cycle enzyme.
    evidence:
    - reference: DOI:10.1128/msystems.00248-24
      notes: Serine-glyoxylate transaminase (SGT) occurs in all 75 organisms; strong
        serine-cycle marker.
    predicate_id: biolink:catalyzes
  - subject: hydroxypyruvate_reductase
    predicate: catalyzes
    object: serine_pathway
    description: HprA/HPR is a ubiquitous serine-cycle enzyme.
    evidence:
    - reference: DOI:10.1128/msystems.00248-24
      notes: Hydroxypyruvate reductase (HPR) is ubiquitous (all 75 genomes); strong
        serine-cycle marker.
    predicate_id: biolink:catalyzes
  - subject: formaldehyde_dehydrogenase
    predicate: oxidizes to
    object: formate
    description: Formaldehyde dehydrogenase oxidizes formaldehyde to formate.
    evidence:
    - reference: DOI:10.1128/msystems.00248-24
      notes: FDH converts formaldehyde to formate in the dissimilatory oxidation branch.
  - subject: formate_dehydrogenase
    predicate: oxidizes to
    object: carbon_dioxide
    description: Formate dehydrogenase oxidizes formate to CO2 completing C1 dissimilation.
    evidence:
    - reference: DOI:10.1007/s00284-022-03141-8
      notes: Oxidation of formaldehyde via H4F/RuMP routes to formate and then to
        CO2; strong downstream dissimilation edge.
  - subject: mxa_methanol_dehydrogenase
    predicate: requires cofactor
    object: pqq
    description: MxaFI methanol dehydrogenase requires the PQQ redox cofactor.
    evidence:
    - reference: DOI:10.1128/msphere.00685-24
      notes: Mxa-type MDHs belong to the PQQ-dependent alcohol dehydrogenase family.
  - subject: mxa_methanol_dehydrogenase
    predicate: requires cofactor
    object: calcium_ion
    description: MxaFI methanol dehydrogenase requires a calcium ion in its active
      site.
    evidence:
    - reference: DOI:10.1016/b978-0-443-13307-7.00014-1
      notes: MxaF contains a calcium ion in its active site.
curation_history:
- timestamp: '2026-05-05T01:35:46.877023+00:00'
  curator: seed_from_metpo
  action: SEEDED_FROM_METPO
  changes: imported from data/raw/metpo.owl (CLASS)
  llm_assisted: false
- timestamp: '2026-05-08T00:00:00-07:00'
  curator: codex
  action: ADDED_CAUSAL_GRAPH
  changes: Added DOI-backed causal graph for methanol oxidation and formaldehyde assimilation
    in methylotrophy.
  llm_assisted: true
- timestamp: '2026-05-20T03:35:31Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2000202×2, METPO:2000016×1).
  llm_assisted: true
- timestamp: '2026-05-20T05:49:25Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (biolink:located_in×1).
  llm_assisted: true
- timestamp: '2026-05-23T21:30:07Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2007405×1).
  llm_assisted: true
- timestamp: '2026-05-24T04:38:01Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (GO:0042597×1).
  llm_assisted: true
- timestamp: '2026-05-24T05:05:15Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv
    (UniProtKB:A0A010SCY7×1, UniProtKB:A0A4U8YZA6×1).
  llm_assisted: true
- timestamp: '2026-06-14T05:51:47Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (GO:0019647×1).
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: ENRICH_CAUSAL_GRAPH
  changes: Added 7 evidence-backed generic edges (10 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-24T17:21:14Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (biolink:catalyzes×3).
  llm_assisted: true
- timestamp: '2026-06-24T17:21:20Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (CHEBI:16526×1).
  llm_assisted: true