fosfomycin

CHEBI:28915 EXACT SEEDED antibacterial

What these status tags mean

Curation status describes a workflow state. SEEDED means the record entered through the source-seeding workflow; it does not imply that no later curation occurred. PROPOSED marks an addition awaiting review; REVIEWED records curator sign-off on identity, structure, filing class and producer claims; DEPRECATED retains a superseded or out-of-scope record. These are workflow decisions, not independently verified human review. Agent-assisted contributions may appear in the record history.

Grounding describes the identifier mapping: EXACT uses an ontology identity asserted by the source; MINTED keeps a local identifier when no defensible ontology identity is available; REVIEW_NEEDED flags an exact structure whose ontology identity needs adjudication. The grounding note retains any unresolved alternatives. These tags do not establish the strength of producer or activity evidence.

A phosphonic acid having an (R,S)-1,2-epoxypropyl group attached to phosphorus.

Structure

Standard InChIKey	YMDXZJFXQJVXBF-STHAYSLISA-N
SMILES	C[C@H]1[C@H](O1)[P](=O)(O)O
Stereochemistry	fully defined
Cross-references	pubchem:73491, pubchem:446987

Filing pathway

Unclassified — computed by NPClassifier npclassifier.gnps2.org@2026-09-07, which is why it is pinned rather than recomputed. The gene cluster's asserted class is other, from MIBiG.

Producer organisms 2

A claim that this taxon makes the compound. The basis says what the evidence addressed — a knockout and a database assertion are not the same claim.

Taxon	Basis	Cluster	Evidence
Streptomyces fradiae NCBITaxon:1906	SOURCE_ASSERTION	mibig:BGC0000938	DOI:10.1016/j.chembiol.2006.09.007
Pseudomonas syringae NCBITaxon:317	SOURCE_ASSERTION	mibig:BGC0001859	PMID:22615277

Occurrences 19

Somebody found the compound in this organism and cited it. That is not a claim that the organism makes it, and nothing here promotes one to the other.

Taxon	Source	Reference
Streptomyces NCBITaxon:1883	LOTUS	DOI:10.1016/J.BMC.2018.05.017
Pseudomonas viridiflava NCBITaxon:33069	LOTUS	DOI:10.7164/ANTIBIOTICS.43.238
Arabidopsis thaliana NCBITaxon:3702	LOTUS	DOI:10.1007/S00425-002-0762-0
Streptomyces wedmorensis NCBITaxon:43759	LOTUS	DOI:10.1007/BF00290527
Streptomyces wedmorensis NCBITaxon:43759	LOTUS	DOI:10.1016/J.ABB.2013.12.004
Streptomyces wedmorensis NCBITaxon:43759	LOTUS	DOI:10.1107/S1744309105012376
Streptomyces wedmorensis NCBITaxon:43759	LOTUS	DOI:10.1128/AAC.44.3.647-650.2000
Streptomyces wedmorensis NCBITaxon:43759	LOTUS	DOI:10.1271/BBB1961.49.873
Streptomyces wedmorensis NCBITaxon:43759	LOTUS	DOI:10.7164/ANTIBIOTICS.44.1286
Streptomyces wedmorensis NCBITaxon:43759	LOTUS	DOI:10.7164/ANTIBIOTICS.45.1008
Streptomyces wedmorensis NCBITaxon:43759	LOTUS	DOI:10.7164/ANTIBIOTICS.45.1812
Streptomyces wedmorensis NCBITaxon:43759	LOTUS	DOI:10.7164/ANTIBIOTICS.49.502
Streptomyces fradiae NCBITaxon:1906	LOTUS	DOI:10.1002/ANIE.199403411
Streptomyces fradiae NCBITaxon:1906	LOTUS	DOI:10.1021/ACS.BIOCHEM.8B00693
Streptomyces fradiae NCBITaxon:1906	LOTUS	DOI:10.1039/P19910001993
Streptomyces fradiae NCBITaxon:1906	LOTUS	DOI:10.1126/SCIENCE.166.3901.122
Streptomyces fradiae NCBITaxon:1906	LOTUS	DOI:10.1128/AAC.5.2.121
Pseudomonas syringae NCBITaxon:317	LOTUS	DOI:10.1128/AAC.06478-11
Pseudomonas syringae NCBITaxon:317	LOTUS	DOI:10.7164/ANTIBIOTICS.39.1011

Biosynthetic gene clusters 2

Accession	Host	Locus evidence	Genome
mibig:BGC0000938	Streptomyces fradiae NCBITaxon:1906	CLUSTER_DEMONSTRATED	genbank:EU924263.1
mibig:BGC0001859	Pseudomonas syringae NCBITaxon:317	CLUSTER_DEMONSTRATED	genbank:JX102649.1

A locus claim and a taxon claim are different questions. Heterologous expression settles the first and leaves the second where the isolation report left it.

Biosynthesis curated

Written by a curator with claim-level evidence on each step; not derived from a source. This is what the rest of the record exists to support.

Step	Enzyme	Reaction	Substrate → product	Evidence
10	Psf1/Psf2 phosphonomethylmalate-forming module		ungrounded → ungrounded	DOI:10.1128/AAC.06478-11
80	Psf3 UniProtKB:I6R485		ungrounded → CHEBI:62246	DOI:10.1021/acschembio.6b00939
90	Ps-HppE UniProtKB:Q9JN69	RHEA:10808	CHEBI:62246 → CHEBI:62247	DOI:10.1021/bi800877v

Step 10: Psf1 and Psf2 together convert phosphoenolpyruvate plus acetyl-CoA into phosphonomethylmalate in the assayed Pseudomonas syringae PB-5123 route. The individual phosphonopyruvate intermediate is not represented as a separate PathwayStep because the source directly detected the two-enzyme Pmm product rather than isolating phosphonopyruvate.

Step 80: This demonstrated Psf3 reaction is the penultimate fosfomycin biosynthetic step in the assayed Pseudomonas syringae PB-5123 route. The exact 2-oxopropylphosphonate substrate is not grounded to a CURIE in this record, so only the ChEBI-grounded (S)-2-HPP product is populated.

Step 90: This deliberately curates only the Pseudomonas syringae PB-5123 Ps-HppE final epoxidation of (S)-2-hydroxypropylphosphonate to the Rhea fosfomycin microspecies; the upstream Pseudomonas and Streptomyces branches remain uncurated.

Mechanism & Biosynthesis Overview

Causal graph — biosynthesis 11 nodes, 9 edges

Partial Pseudomonas syringae fosfomycin biosynthesis graph for Psf1/Psf2 phosphonomethylmalate formation, Psf3 reduction of 2-oxopropylphosphonate to (S)-2-hydroxypropylphosphonate, and the Ps-HppE-catalyzed final epoxidation of (S)-2-hydroxypropylphosphonate.

Subject	Predicate	Object	Notes	Evidence
phosphoenolpyruvate	participates in	phosphonomethylmalate formation		DOI:10.1128/AAC.06478-11 reference DOI:10.1128/AAC.06478-11 evidence type PRIMARY_EXPERIMENT snippet When either Psf1 or Psf2 was omitted notes Kim et al. cloned psf1 and psf2 from the Pseudomonas syringae PB-5123 fosfomycin cluster, purified His-tagged Psf1 and Psf2, and found that the combined PEP, acetyl-CoA, Psf1, and Psf2 assay formed phosphonomethylmalate; omission of either enzyme prevented new phosphonate product formation.
acetyl-CoA	participates in	phosphonomethylmalate formation		DOI:10.1128/AAC.06478-11 reference DOI:10.1128/AAC.06478-11 evidence type PRIMARY_EXPERIMENT snippet When either Psf1 or Psf2 was omitted notes Kim et al. cloned psf1 and psf2 from the Pseudomonas syringae PB-5123 fosfomycin cluster, purified His-tagged Psf1 and Psf2, and found that the combined PEP, acetyl-CoA, Psf1, and Psf2 assay formed phosphonomethylmalate; omission of either enzyme prevented new phosphonate product formation.
Psf1	catalyzes	phosphonomethylmalate formation		DOI:10.1128/AAC.06478-11 https://www.uniprot.org/uniprotkb/I6QN26 https://www.ncbi.nlm.nih.gov/protein/AFM38986.1 reference DOI:10.1128/AAC.06478-11 evidence type PRIMARY_EXPERIMENT snippet When either Psf1 or Psf2 was omitted notes Kim et al. cloned psf1 and psf2 from the Pseudomonas syringae PB-5123 fosfomycin cluster, purified His-tagged Psf1 and Psf2, and found that the combined PEP, acetyl-CoA, Psf1, and Psf2 assay formed phosphonomethylmalate; omission of either enzyme prevented new phosphonate product formation. reference https://www.uniprot.org/uniprotkb/I6QN26 evidence type DATABASE_ASSERTION retrieved on 2026-09-28 notes UniProtKB:I6QN26 is the unreviewed 291 aa Pseudomonas syringae phosphoenolpyruvate mutase entry and cross-references EMBL JX102649 protein AFM38986.1. reference https://www.ncbi.nlm.nih.gov/protein/AFM38986.1 evidence type DATABASE_ASSERTION snippet product="phosphoenolpyruvate phosphomutase" retrieved on 2026-09-28 notes NCBI GenPept AFM38986.1 is the JX102649.1 Psf1 coding sequence from the Pseudomonas syringae PB-5123 fosfomycin cluster.
Psf2	catalyzes	phosphonomethylmalate formation		DOI:10.1128/AAC.06478-11 https://www.uniprot.org/uniprotkb/I6QY75 https://www.ncbi.nlm.nih.gov/protein/AFM38993.1 reference DOI:10.1128/AAC.06478-11 evidence type PRIMARY_EXPERIMENT snippet When either Psf1 or Psf2 was omitted notes Kim et al. cloned psf1 and psf2 from the Pseudomonas syringae PB-5123 fosfomycin cluster, purified His-tagged Psf1 and Psf2, and found that the combined PEP, acetyl-CoA, Psf1, and Psf2 assay formed phosphonomethylmalate; omission of either enzyme prevented new phosphonate product formation. reference https://www.uniprot.org/uniprotkb/I6QY75 evidence type DATABASE_ASSERTION retrieved on 2026-09-28 notes UniProtKB:I6QY75 is the unreviewed 380 aa Pseudomonas syringae entry that cross-references EMBL JX102649 protein AFM38993.1; GenBank annotates that exact CDS as Psf2. reference https://www.ncbi.nlm.nih.gov/protein/AFM38993.1 evidence type DATABASE_ASSERTION snippet note="Psf2" retrieved on 2026-09-28 notes NCBI GenPept AFM38993.1 is the JX102649.1 Psf2 coding sequence from the Pseudomonas syringae PB-5123 fosfomycin cluster.
phosphonomethylmalate formation	produces	phosphonomethylmalate		DOI:10.1128/AAC.06478-11 reference DOI:10.1128/AAC.06478-11 evidence type PRIMARY_EXPERIMENT snippet When either Psf1 or Psf2 was omitted notes Kim et al. cloned psf1 and psf2 from the Pseudomonas syringae PB-5123 fosfomycin cluster, purified His-tagged Psf1 and Psf2, and found that the combined PEP, acetyl-CoA, Psf1, and Psf2 assay formed phosphonomethylmalate; omission of either enzyme prevented new phosphonate product formation.
2-oxopropylphosphonate	is reduced by	Psf3		DOI:10.1021/acschembio.6b00939 https://www.uniprot.org/uniprotkb/I6R485 https://www.ncbi.nlm.nih.gov/protein/AFM38992.1 reference DOI:10.1021/acschembio.6b00939 evidence type PRIMARY_EXPERIMENT snippet Psf3 carried out the reduction of 2-OPP notes Olivares et al. expressed and purified Pseudomonas syringae PB-5123 Psf3 and showed that it catalyzes the NADPH-dependent reduction of 2-oxopropylphosphonate to (S)-2-hydroxypropylphosphonate. reference https://www.uniprot.org/uniprotkb/I6R485 evidence type DATABASE_ASSERTION retrieved on 2026-09-29 notes UniProtKB:I6R485 is the unreviewed 295 aa Pseudomonas syringae entry that cross-references EMBL JX102649 protein AFM38992.1 and PDB 5U5G from the Psf3 structure. reference https://www.ncbi.nlm.nih.gov/protein/AFM38992.1 evidence type DATABASE_ASSERTION snippet name="Psf3" retrieved on 2026-09-29 notes NCBI GenPept AFM38992.1 is the JX102649.1 Psf3 coding sequence from the Pseudomonas syringae PB-5123 fosfomycin cluster.
Psf3	forms	(S)-2-hydroxypropylphosphonate		DOI:10.1021/acschembio.6b00939 https://www.uniprot.org/uniprotkb/I6R485 https://www.ncbi.nlm.nih.gov/protein/AFM38992.1 reference DOI:10.1021/acschembio.6b00939 evidence type PRIMARY_EXPERIMENT snippet Psf3 carried out the reduction of 2-OPP notes Olivares et al. expressed and purified Pseudomonas syringae PB-5123 Psf3 and showed that it catalyzes the NADPH-dependent reduction of 2-oxopropylphosphonate to (S)-2-hydroxypropylphosphonate. reference https://www.uniprot.org/uniprotkb/I6R485 evidence type DATABASE_ASSERTION retrieved on 2026-09-29 notes UniProtKB:I6R485 is the unreviewed 295 aa Pseudomonas syringae entry that cross-references EMBL JX102649 protein AFM38992.1 and PDB 5U5G from the Psf3 structure. reference https://www.ncbi.nlm.nih.gov/protein/AFM38992.1 evidence type DATABASE_ASSERTION snippet name="Psf3" retrieved on 2026-09-29 notes NCBI GenPept AFM38992.1 is the JX102649.1 Psf3 coding sequence from the Pseudomonas syringae PB-5123 fosfomycin cluster.
(S)-2-hydroxypropylphosphonate	is epoxidized by	Ps-HppE		DOI:10.1021/bi800877v DOI:10.1128/AAC.06478-11 https://www.uniprot.org/uniprotkb/Q9JN69 https://www.ncbi.nlm.nih.gov/protein/AFM38989.1 reference DOI:10.1021/bi800877v evidence type PRIMARY_EXPERIMENT snippet This purified P. syringae protein was determined to catalyze the epoxidation of ( S)-HPP to fosfomycin notes Munos et al. purified Pseudomonas syringae Ps-HppE and showed that it catalyzes the final HPP-to-fosfomycin epoxidation. reference DOI:10.1128/AAC.06478-11 evidence type PRIMARY_EXPERIMENT snippet We sequenced the biosynthetic gene cluster responsible for fosfomycin production in Pseudomonas syringae PB-5123 notes Kim et al. sequenced the Pseudomonas syringae PB-5123 fosfomycin cluster now represented by GenBank JX102649.1. reference https://www.uniprot.org/uniprotkb/Q9JN69 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes Reviewed UniProtKB:Q9JN69 is Pseudomonas syringae Ps-HppE, cross-references EMBL JX102649 protein AFM38989.1, and annotates RHEA:10808 with ChEBI participants CHEBI:62246 and CHEBI:62247. reference https://www.ncbi.nlm.nih.gov/protein/AFM38989.1 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes NCBI GenPept AFM38989.1 is the JX102649.1 Psf4 epoxidase coding sequence from the Pseudomonas syringae PB-5123 fosfomycin cluster.
Ps-HppE	forms	(1R,2S)-epoxypropylphosphonate(1-)	CHEBI:62247 is the Rhea product for fosfomycin; the NaturalProductMech record itself is neutral CHEBI:28915.	DOI:10.1021/bi800877v DOI:10.1128/AAC.06478-11 https://www.uniprot.org/uniprotkb/Q9JN69 https://www.ncbi.nlm.nih.gov/protein/AFM38989.1 reference DOI:10.1021/bi800877v evidence type PRIMARY_EXPERIMENT snippet This purified P. syringae protein was determined to catalyze the epoxidation of ( S)-HPP to fosfomycin notes Munos et al. purified Pseudomonas syringae Ps-HppE and showed that it catalyzes the final HPP-to-fosfomycin epoxidation. reference DOI:10.1128/AAC.06478-11 evidence type PRIMARY_EXPERIMENT snippet We sequenced the biosynthetic gene cluster responsible for fosfomycin production in Pseudomonas syringae PB-5123 notes Kim et al. sequenced the Pseudomonas syringae PB-5123 fosfomycin cluster now represented by GenBank JX102649.1. reference https://www.uniprot.org/uniprotkb/Q9JN69 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes Reviewed UniProtKB:Q9JN69 is Pseudomonas syringae Ps-HppE, cross-references EMBL JX102649 protein AFM38989.1, and annotates RHEA:10808 with ChEBI participants CHEBI:62246 and CHEBI:62247. reference https://www.ncbi.nlm.nih.gov/protein/AFM38989.1 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes NCBI GenPept AFM38989.1 is the JX102649.1 Psf4 epoxidase coding sequence from the Pseudomonas syringae PB-5123 fosfomycin cluster.

Every edge carries its own citation; an uncited edge is refused by the corpus tests.

Elsewhere in the fleet

AntibioticMech — CHEBI:28915 (same structure, same inchikey)

Explore across X-Mech

AntibioticMech (fosfomycin) ↗ MediaIngredientMech (CHEBI:28915) ↗ TaxonMech: Streptomyces fradiae (NCBITaxon:1906) ↗ TaxonMech: Pseudomonas syringae (NCBITaxon:317) ↗ PathwayMech (mibig:BGC0000938) ↗ PathwayMech (mibig:BGC0001859) ↗

Open questions 1

shared-structure — This structure is reported by more than one MIBiG entry: BGC0000938, BGC0001859. Confirm they describe the same compound rather than an upstream cross-reference error.

Provenance

Source concept	Source	Version
BGC0000938	MIBIG	5
BGC0001859	MIBIG	4
CHEBI:28915	CHEBI	3-star

This page is generated from data/natural_products/unclassified/fosfomycin.yaml, which is generated from the committed inventories. Neither is edited by hand.