methylotrophic

METPO:1000651 · CLASS · REVIEWED

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

Trait evidence (1)

DOI:10.3389/fbioe.2021.787791
methanol utilization in methylotrophy

Review supports methanol oxidation and formaldehyde assimilation as central methylotrophy mechanisms.

Methanol-based methylotrophy mechanism

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

MECHANISTIC · This graph combines alternative RuMP and serine assimilation branches and several methanol/formaldehyde oxidation enzyme classes. The AM1 MxaF accession anchors only the calcium-dependent MxaFI branch and is one subunit, not the complete heterotetramer.

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.
MxaFI methanol dehydrogenase example of PQQ-dependent methanol dehydrogenase rdfs:subClassOf
The calcium-dependent Mxa enzyme is a PQQ-dependent alcohol dehydrogenase used for methanol oxidation.
- DOI:10.1128/msphere.00685-24 Xox- and Mxa-type MDHs belong to the diverse group of pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenases Verified against the open mSphere primary article.
formaldehyde oxidized by formaldehyde dehydrogenase (Fld/FDH)
Formaldehyde dehydrogenase oxidizes formaldehyde to formate in the dissimilatory branch.
- DOI:10.3109/10409238.2012.697865 formaldehyde is then oxidized to formate Verified against the public full text.
formate oxidized by formate dehydrogenase (Fdh)
Formate dehydrogenase continues C1 dissimilation by oxidizing formate to carbon dioxide.
- DOI:10.3109/10409238.2012.697865 formate and carbon dioxide by formaldehyde and formate dehydrogenases, respectively Verified against the public full text.

Protein and taxon examples

Graph node Protein Taxon UniProt status Role and evidence

MxaFI methanol dehydrogenase

Graph node	Protein	Taxon	UniProt status	Role and evidence
MxaFI methanol dehydrogenase	`UniProtKB:P16027` Methanol dehydrogenase [cytochrome c] subunit 1 (mxaF)	Methylorubrum extorquens AM1 `NCBITaxon:272630`	`REVIEWED` retrieved 2026-08-24 · entry v179 · sequence v1	Large catalytic MxaF component of the AM1 MxaFI methanol dehydrogenase; this accession is not presented as the complete enzyme. `DOI:10.1016/0378-1119(90)90457-3` AM1 moxF and moxJ genes are involved in methanol oxidation The primary sequence study identifies the AM1 moxF/mxaF gene in methanol oxidation; UniProt verifies reviewed P16027 and the strain taxon.

UniProtKB:P16027
Methanol dehydrogenase [cytochrome c] subunit 1 (mxaF)

Methylorubrum extorquens AM1
NCBITaxon:272630

REVIEWED
retrieved 2026-08-24 · entry v179 · sequence v1

Large catalytic MxaF component of the AM1 MxaFI methanol dehydrogenase; this accession is not presented as the complete enzyme.

DOI:10.1016/0378-1119(90)90457-3 AM1 moxF and moxJ genes are involved in methanol oxidation The primary sequence study identifies the AM1 moxF/mxaF gene in methanol oxidation; UniProt verifies reviewed P16027 and the strain taxon.

Provenance

Identifier source: METPO (2026-06-12)
Definition source: DOI:10.3389/fbioe.2021.787791

Parent traits (1)

trophic type METPO:1000631

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).

physiology trophic type 0.398
metabolism Acetogenesis 0.387
physiology carboxydotrophic 0.374
physiology photolithoautotrophic 0.373
physiology hydrogenotrophic 0.371
physiology lithoautotrophic 0.358
physiology lithoheterotrophic 0.345
physiology chemoautotrophic 0.340

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.

Canonical examples (2)

Organisms cited as exemplars of this trait. Taxon ids are NCBITaxon and link out to the NCBI record.

Methylorubrum extorquens NCBITaxon:408 PMID:12730156 Model facultative methylotroph (formerly Methylobacterium extorquens; strain AM1).
Methylorubrum extorquens AM1 NCBITaxon:272630 DOI:10.1016/0378-1119(90)90457-3 Strain-level facultative methylotroph paired to reviewed MxaF, the large catalytic component of its MxaFI methanol dehydrogenase.

Curation history

2026-08-25T00:00:00-07:00 · REVIEW_ONTOLOGY_GROUNDINGS · codex
Retracted obsolete GO:0019647 from the ribulose monophosphate cycle node. GO replaced it with broader GO:0019649 formaldehyde assimilation, which is already represented by a separate graph node and is not an exact grounding for this named pathway variant.
2026-05-05T01:35:46.877023+00:00 · SEEDED_FROM_METPO · seed_from_metpo
imported from data/raw/metpo.owl (CLASS)
2026-05-08T00:00:00-07:00 · ADDED_CAUSAL_GRAPH · codex
Added DOI-backed causal graph for methanol oxidation and formaldehyde assimilation in methylotrophy.
2026-05-20T03:35:31Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2000202×2, METPO:2000016×1).
2026-05-20T05:49:25Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (biolink:located_in×1).
2026-05-23T21:30:07Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2007405×1).
2026-05-24T04:38:01Z · GROUND_CAUSAL_NODES · claude
Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0042597×1).
2026-05-24T05:05:15Z · GROUND_CAUSAL_NODES · claude
Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (UniProtKB:A0A010SCY7×1, UniProtKB:A0A4U8YZA6×1).
2026-06-14T05:51:47Z · GROUND_CAUSAL_NODES · claude
Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0019647×1).
2026-06-23T00:00:00Z · ENRICH_CAUSAL_GRAPH · claude
Added 7 evidence-backed generic edges (10 new nodes) from the deep-research report.
2026-06-24T17:21:14Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (biolink:catalyzes×3).
2026-06-24T17:21:20Z · GROUND_CAUSAL_NODES · claude
Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:16526×1).
2026-07-20T04:21:12Z · 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)
2026-07-20T04:23:55Z · GROUND_CAUSAL_NODES · claude
Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0009326×1).
2026-08-06T01:00:00Z · 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.
2026-08-06T02:00:00Z · 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.
2026-08-26T03:23:00Z · CURATE_PROTEIN_TAXON_EXAMPLE · claude
Backfilled provenance (review issue 517) for the codex protein-taxon review tranche of 2026-08-24/25, which shipped without a per-record event. In this record the tranche: set graph scope methylotrophic_methanol_assimilation=MECHANISTIC with scope_notes; marked 7 GENE_OR_PROTEIN node(s) REVIEWED_LABEL_ONLY with grounding_notes (methanol_dehydrogenase, pqq_dependent_mdh, hexulose_phosphate_synthase, serine_glyoxylate_aminotransferase, hydroxypyruvate_reductase, formaldehyde_dehydrogenase, mxa_methanol_dehydrogenase); added taxon-paired protein example(s) UniProtKB:P16027 on mxa_methanol_dehydrogenase (NCBITaxon:272630); added canonical example(s) NCBITaxon:272630.
2026-08-31T11:15:00Z · CONNECT_CAUSAL_GRAPH_COMPONENTS · codex
Resolved issue #183 graph fragmentation (4 components to 1) with 3 public-source, verbatim-snippet-backed connector(s). No paid research service was called.