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methylotrophic

METPO:1000651 · CLASS · REVIEWED

A trophic type in which an organism obtains energy and carbon from reduced one-carbon compounds.

Methanol-based methylotrophy mechanism

DOI-backed graph for methanol oxidation to formaldehyde and assimilation through native methylotrophy pathways.

Methanol-based methylotrophy mechanism Interactive directed graph showing evidence-backed causal relationships for methylotrophic.

Edge evidence

  • methylotrophic uses substrate methanol

    Methanol is a representative reduced C1 substrate for methylotrophy.

    • DOI:10.3389/fbioe.2021.787791 methanol utilization in methylotrophy Supports methanol as a methylotrophic substrate; other C1 substrates are not modeled here.
  • methanol dehydrogenase oxidizes methanol METPO:2007803

    Methanol dehydrogenase catalyzes the first methanol oxidation step.

    • DOI:10.3389/fbioe.2021.787791 Mdh is a primary enzyme Supports methanol dehydrogenase as the primary methanol-utilization enzyme.
  • methanol oxidized to formaldehyde METPO:2007405

    Methanol oxidation produces formaldehyde for assimilation or further oxidation.

    • DOI:10.3389/fbioe.2021.787791 converts methanol to formaldehyde Supports methanol-to-formaldehyde conversion.
  • PQQ-dependent methanol dehydrogenase located in periplasmic space biolink:located_in

    PQQ-dependent MDH oxidizes methanol in the periplasm of Gram-negative methylotrophs.

    • DOI:10.3389/fbioe.2021.787791 oxidation of methanol occurs in the periplasmic space Supports periplasmic localization of PQQ-dependent methanol oxidation.
  • PQQ-dependent methanol dehydrogenase produces formaldehyde METPO:2007800

    PQQ-dependent methanol dehydrogenase produces formaldehyde from methanol.

    • DOI:10.3389/fbioe.2021.787791 converts methanol to formaldehyde Source supports formaldehyde as the product of methanol oxidation by methanol dehydrogenases.
  • formaldehyde assimilated by ribulose monophosphate cycle

    Formaldehyde can enter the RuMP cycle for growth on methanol.

    • DOI:10.3389/fbioe.2021.787791 ribulose monophosphate (RuMP) cycle Supports RuMP as a native formaldehyde assimilation pathway.
  • formaldehyde assimilated by serine pathway

    Formaldehyde can enter the serine pathway for growth on methanol.

    • DOI:10.3389/fbioe.2021.787791 serine pathway Supports the serine pathway as a native formaldehyde assimilation route.
  • ribulose monophosphate cycle has output biomass precursor RO:0002234

    RuMP assimilation incorporates C1 carbon into cellular material.

    • DOI:10.3389/fbioe.2021.787791 growth support of microorganisms in methanol Supports assimilation pathways as growth-supporting routes.
  • 3-hexulose-6-phosphate synthase (Hps) catalyzes ribulose monophosphate cycle biolink:catalyzes

    Hps drives formaldehyde assimilation in the RuMP cycle.

    • DOI:10.1038/s41467-023-43610-7 The RuMP pathway relies on 3-hexulose 6-phosphate synthase (Hps) and phosphohexose isomerase (Phi) to assimilate formaldehyde.
  • serine-glyoxylate aminotransferase (SgaA/SGT) catalyzes serine pathway biolink:catalyzes

    SgaA/SGT is a conserved serine-cycle enzyme.

    • DOI:10.1128/msystems.00248-24 Serine-glyoxylate transaminase (SGT) occurs in all 75 organisms; strong serine-cycle marker.
  • hydroxypyruvate reductase (HprA/HPR) catalyzes serine pathway biolink:catalyzes

    HprA/HPR is a ubiquitous serine-cycle enzyme.

    • DOI:10.1128/msystems.00248-24 Hydroxypyruvate reductase (HPR) is ubiquitous (all 75 genomes); strong serine-cycle marker.
  • formaldehyde dehydrogenase (Fld/FDH) oxidizes to formate

    Formaldehyde dehydrogenase oxidizes formaldehyde to formate.

    • DOI:10.1128/msystems.00248-24 FDH converts formaldehyde to formate in the dissimilatory oxidation branch.
  • formate dehydrogenase (Fdh) oxidizes to carbon dioxide

    Formate dehydrogenase oxidizes formate to CO2 completing C1 dissimilation.

    • DOI:10.1007/s00284-022-03141-8 Oxidation of formaldehyde via H4F/RuMP routes to formate and then to CO2; strong downstream dissimilation edge.
  • MxaFI methanol dehydrogenase requires cofactor pyrroloquinoline quinone (PQQ)

    MxaFI methanol dehydrogenase requires the PQQ redox cofactor.

    • DOI:10.1128/msphere.00685-24 Mxa-type MDHs belong to the PQQ-dependent alcohol dehydrogenase family.
  • MxaFI methanol dehydrogenase requires cofactor calcium ion (Ca2+)

    MxaFI methanol dehydrogenase requires a calcium ion in its active site.

    • DOI:10.1016/b978-0-443-13307-7.00014-1 MxaF contains a calcium ion in its active site.

Provenance

Source
METPO (2025-11-25)
Definition source
DOI:10.3389/fbioe.2021.787791

Parent traits (1)

Synonyms (3)

  • TT_methylotroph RELATED_SYNONYM · metpo.owl
  • methylotroph RELATED_SYNONYM · metpo.owl
  • methylotrophy RELATED_SYNONYM · metpo.owl

kg-microbe context

Matched 1 kg-microbe node via direct_metpo.

  • METPO:1000651 [-1.480, -2.354, -1.736, -0.358, …]

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/physiology/methylotrophic-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. 
# Curation-focused research report: methylotrophic

## Executive curation recommendation

**Trait:** methylotrophic  
**Trait identifier:** `METPO:1000651`  
**Category:** PHYSIOLOGY; **term kind:** CLASS; **mapping:** REVIEWED  
**Parent:** `METPO:1000631`

The trait should represent the demonstrated capacity to obtain **both cellular carbon and energy from reduced one-carbon compounds**, generally compounds lacking carbon–carbon bonds. The most defensible generic causal architecture is:

**reduced C1 substrate → substrate-specific oxidation/transfer module → assimilatory C1 flux + energy-conserving oxidation → biomass formation and growth on the C1 substrate.**

Methylotrophy is mechanistically diverse rather than a single pathway. Therefore, the graph should use alternative modules for methanol, methylamine, and other reduced C1 substrates, converging on formaldehyde/formate-level metabolism, assimilation, energy conservation, and growth. Methanol oxidation followed by formaldehyde assimilation is a strong core example, but it must not define the entire trait. The authoritative modern definition distinguishes methylotrophy from **methylovory**, in which a C1 compound supplements energy without supplying the organism’s carbon requirement. Methanotrophs are methylotrophs that can use methane, but non-methanotrophic methylotrophs use substrates such as methanol or methylamine without oxidizing methane (chistoserdova2018currenttrendsin pages 3-4, chistoserdova2018currenttrendsin pages 2-3).

## 1. Scope and boundaries

### Included phenotype

A positive phenotype requires evidence of growth, biomass carbon incorporation, or a comparably strong physiological demonstration that a reduced C1 compound serves as both carbon and energy source. Suitable assays include growth with methanol or methylamine as the sole carbon and energy source, isotope incorporation into biomass coupled to oxidation, or genetic loss-and-rescue experiments that connect a C1 pathway to growth.

### Important boundary cases

1. **Methanotrophy:** methane-utilizing organisms are a substrate-defined subset of methylotrophs. Methane monooxygenase belongs in a methane-specific upstream extension, not in the universal methylotrophy core.
2. **Methylovory:** supplemental oxidation of a C1 compound for energy, without C1-derived biomass carbon, is insufficient. This is explicitly distinguished from methylotrophy in current expert reviews (chistoserdova2018currenttrendsin pages 2-3, wegner2019lanthanidedependentmethylotrophsof pages 2-3).
3. **Formaldehyde detoxification:** glutathione-dependent or other formaldehyde-removal systems occur in many non-methylotrophs. Detoxification alone does not establish methylotrophy.
4. **Methylamine as nitrogen only:** methylamine utilization for nitrogen, with succinate or another multicarbon carbon source, is not a methylotrophic growth phenotype. In *Methylobacterium extorquens* AM1, MaDH and N-methylglutamate pathways can be differentially favored for methylamine as carbon/energy versus nitrogen (nayak2016selectionmaintainsapparently pages 8-9).
5. **Genomic potential:** an isolated `xoxF`, `mxaF`, formaldehyde-dehydrogenase gene, or incomplete pathway is not proof of growth. Some XoxF-containing organisms lack recognizable assimilation modules, and environmental studies commonly infer rather than demonstrate activity (chistoserdova2018currenttrendsin pages 2-3, voutsinos2024weatheredgranitesand pages 2-4).
6. **Synthetic methylotrophy:** engineered methanol incorporation should be described as synthetic or partial unless methanol supports net growth as the carbon and energy source.
7. **Methyl-based methanogenesis:** archaeal conversion of methyl compounds to methane is often called “methylotrophic methanogenesis,” but it is not automatically equivalent to the aerobic bacterial trophic phenotype modeled here. It should be represented only if TraitMech explicitly intends a cross-domain, process-neutral scope.

## 2. Candidate causal-graph nodes

Identifiers below are limited to source-reported or readily verifiable stable classes. Where exact ontology mapping has not been checked against the project’s preferred release, a label-only node is safer than an invented CURIE.

### Trait and phenotype nodes

- `METPO:1000651` — methylotrophic
- growth on reduced one-carbon compound
- C1-derived biomass formation
- C1-dependent energy conservation
- methylovory — boundary/negative comparator
- formaldehyde tolerance — accessory phenotype, not equivalent to methylotrophy

### Substrates, products, and intermediates

- methanol
- methylamine
- methane — substrate-specific upstream extension
- formaldehyde
- formate/formic acid
- carbon dioxide
- ammonium
- glycine; L-serine; hydroxypyruvate; D-glycerate
- ribulose 5-phosphate; hexulose 6-phosphate; fructose 6-phosphate
- 5,10-methylene-tetrahydrofolate; tetrahydrofolate
- acetyl-CoA; glyoxylate; malyl-CoA; ethylmalonyl-CoA
- NAD+/NADH; PQQ/PQQH2
- molecular oxygen; hydrogen peroxide

Showing the first 60 of 303 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 methanol oxidation and formaldehyde assimilation in methylotrophy.

  3. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2000202×2, METPO:2000016×1).

  4. · GROUND_CAUSAL_PREDICATES · claude

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

  5. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2007405×1).

  6. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0042597×1).

  7. · GROUND_CAUSAL_NODES · claude

    Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A010SCY7×1, UniProtKB:A0A4U8YZA6×1).

  8. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0019647×1).

  9. · ENRICH_CAUSAL_GRAPH · claude

    Added 7 evidence-backed generic edges (10 new nodes) from the deep-research report.

  10. · GROUND_CAUSAL_PREDICATES · claude

    Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (biolink:catalyzes×3).

  11. · GROUND_CAUSAL_NODES · claude

    Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:16526×1).

  12. · RETRACT_DEAD_UNIPROT_GROUNDINGS · claude

    Retracted 2 UniProtKB grounding(s) whose accessions are deleted from UniProt; nodes demoted to label-only pending re-grounding (docs/GROUNDING_POLICY.md)

  13. · GROUND_CAUSAL_NODES · claude

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

  14. · 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.

  15. · MIGRATE_MICROBE_DOMAIN_EDGES_PART2 · claude

    Re-grounded 2 causal edge(s) off microbe-domain METPO predicates onto their causal-graph counterparts (1 to oxidizes, 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.