epothilone B
CHEBI:31550 EXACT SEEDED cytotoxicenzyme inhibitor
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REVIEWED records curator sign-off on identity, structure, filing class and producer claims; DEPRECATED retains a superseded or out-of-scope record.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.
An epithilone that is epithilone D in which the double bond in the macrocyclic ring has been oxidised to the corresponding epoxide (the S,S stereoisomer).
Structure
| Standard InChIKey | QXRSDHAAWVKZLJ-PVYNADRNSA-N |
|---|---|
| SMILES | C[C@H]1CCC[C@@]2(C)O[C@H]2C[C@H](OC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@H]1O)C(\C)=C\C1=CSC(C)=N1 |
| Stereochemistry | fully defined |
| Cross-references | npatlas:NPA06085, pubchem:448013 |
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 nrps, pks, from MIBiG.
Producer organisms 4
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 |
|---|---|---|---|
| Sorangium cellulosum NCBITaxon:56 |
SOURCE_ASSERTION | mibig:BGC0000988 | PMID:10662695 |
| Sorangium cellulosum So0157-2 NCBITaxon:1254432 |
SOURCE_ASSERTION | mibig:BGC0000989 | PMID:23549746 |
| Sorangium cellulosum NCBITaxon:56 |
SOURCE_ASSERTION | mibig:BGC0000990 | PMID:10662695 |
| Sorangium cellulosum NCBITaxon:56 |
SOURCE_ASSERTION | mibig:BGC0000991 | PMID:10649995 |
Occurrences 11
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 |
|---|---|---|
| Microporus NCBITaxon:1191098 |
LOTUS | DOI:10.1021/ACS.JNATPROD.7B00764 |
| Sparticola junci NCBITaxon:1803578 |
LOTUS | DOI:10.1021/ACS.JNATPROD.9B00604 |
| Nocardiopsis NCBITaxon:2013 |
LOTUS | DOI:10.1021/ACS.JNATPROD.8B00708 |
| Sporormiella similis NCBITaxon:269685 |
LOTUS | DOI:10.1021/ACS.JNATPROD.7B00064 |
| Sorangium NCBITaxon:39643 |
LOTUS | DOI:10.1021/NP000629F |
| Sorangium cellulosum NCBITaxon:56 |
LOTUS | DOI:10.1002/ANIE.199615671 |
| Sorangium cellulosum NCBITaxon:56 |
LOTUS | DOI:10.1007/S00253-013-4830-0 |
| Sorangium cellulosum NCBITaxon:56 |
LOTUS | DOI:10.1016/S0378-1119(00)00149-9 |
| Sorangium cellulosum NCBITaxon:56 |
LOTUS | DOI:10.1016/S1074-5521(00)00075-2 |
| Sorangium cellulosum NCBITaxon:56 |
LOTUS | DOI:10.1021/NP000629F |
| Sorangium cellulosum NCBITaxon:56 |
LOTUS | DOI:10.7164/ANTIBIOTICS.49.560 |
Biosynthetic gene clusters 4
| Accession | Host | Locus evidence | Genome |
|---|---|---|---|
| mibig:BGC0000988 | Sorangium cellulosum NCBITaxon:56 |
CLUSTER_UNSTATED | genbank:AF210843.1 |
| mibig:BGC0000989 | Sorangium cellulosum So0157-2 NCBITaxon:1254432 |
CLUSTER_UNSTATED | genbank:EU414841.1 |
| mibig:BGC0000990 | Sorangium cellulosum NCBITaxon:56 |
CLUSTER_UNSTATED | genbank:GU063811.1 |
| mibig:BGC0000991 | Sorangium cellulosum NCBITaxon:56 |
CLUSTER_UNSTATED | genbank:AF217189.1 |
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 |
|---|---|---|---|---|
| 1 | EpoK epothilone C/D epoxidase UniProtKB:Q9KIZ4 |
RHEA:47808 | CHEBI:29579 → CHEBI:31550 | DOI:10.1016/S0378-1119(00)00149-9 |
Step 1: EpoK is the cytochrome P450 epoxidase that carries out terminal epoxidation of epothilone D to epothilone B; RHEA:47808 grounds the full reduced-ferredoxin-dependent monooxygenase reaction.
Mechanism & Biosynthesis Overview
Causal graph — biosynthesis 3 nodes, 2 edges
Partial S. cellulosum epothilone B biosynthesis graph for EpoK-catalyzed terminal epoxidation.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| epothilone D | is epoxidized by | EpoK epothilone C/D epoxidase | EpoK epoxidizes the 12,13-alkene of epothilone D. | DOI:10.1016/S0378-1119(00)00149-9 |
| EpoK epothilone C/D epoxidase | forms | epothilone B | The EpoK cytochrome P450 reaction forms epothilone B as the epoxidized product. | DOI:10.1016/S0378-1119(00)00149-9 |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — biosynthesis 8 nodes, 7 edges
Six source-annotated SMP44 assembly proteins, mapped to complete native AF217189.1 CDS sequences. Five PKS references and one NRPS reference contribute to an epothilone assembly process, without an inferred protein-to-protein reaction chain. The named epothilone B association is supported by the abstract-level whole-cluster result and a separately verified MIBiG structure link. Source-annotated assembly participation, not independently assayed catalysis. No direct protein-to-final-product reaction, exact intermediate, stoichiometry, substrate specificity, physical complex or complete reaction order is asserted. GROUNDED denotes identifier identity, not experimental validation. SMP44 references are not interchangeable with So0157-2 proteins, whose epo gene names differ.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| EpoA (PKS, SMP44 reference) | has_source_annotated_assembly_role_in | SMP44 epothilone core assembly | Source-annotated assembly participation, not independently assayed catalysis. No direct protein-to-final-product reaction, exact intermediate, stoichiometry, substrate specificity, physical complex or complete reaction order is asserted. GROUNDED denotes identifier identity, not experimental validation. SMP44 references are not interchangeable with So0157-2 proteins, whose epo gene names differ. | https://www.ebi.ac.uk/ena/browser/view/AF217189.1 |
| EpoB (NRPS, SMP44 reference) | has_source_annotated_assembly_role_in | SMP44 epothilone core assembly | Source-annotated assembly participation, not independently assayed catalysis. No direct protein-to-final-product reaction, exact intermediate, stoichiometry, substrate specificity, physical complex or complete reaction order is asserted. GROUNDED denotes identifier identity, not experimental validation. SMP44 references are not interchangeable with So0157-2 proteins, whose epo gene names differ. | https://www.ebi.ac.uk/ena/browser/view/AF217189.1 |
| EpoC (PKS, SMP44 reference) | has_source_annotated_assembly_role_in | SMP44 epothilone core assembly | Source-annotated assembly participation, not independently assayed catalysis. No direct protein-to-final-product reaction, exact intermediate, stoichiometry, substrate specificity, physical complex or complete reaction order is asserted. GROUNDED denotes identifier identity, not experimental validation. SMP44 references are not interchangeable with So0157-2 proteins, whose epo gene names differ. | https://www.ebi.ac.uk/ena/browser/view/AF217189.1 |
| EpoD (PKS, SMP44 reference) | has_source_annotated_assembly_role_in | SMP44 epothilone core assembly | Source-annotated assembly participation, not independently assayed catalysis. No direct protein-to-final-product reaction, exact intermediate, stoichiometry, substrate specificity, physical complex or complete reaction order is asserted. GROUNDED denotes identifier identity, not experimental validation. SMP44 references are not interchangeable with So0157-2 proteins, whose epo gene names differ. | https://www.ebi.ac.uk/ena/browser/view/AF217189.1 |
| EpoE (PKS, SMP44 reference) | has_source_annotated_assembly_role_in | SMP44 epothilone core assembly | Source-annotated assembly participation, not independently assayed catalysis. No direct protein-to-final-product reaction, exact intermediate, stoichiometry, substrate specificity, physical complex or complete reaction order is asserted. GROUNDED denotes identifier identity, not experimental validation. SMP44 references are not interchangeable with So0157-2 proteins, whose epo gene names differ. | https://www.ebi.ac.uk/ena/browser/view/AF217189.1 |
| EpoF (PKS, SMP44 reference) | has_source_annotated_assembly_role_in | SMP44 epothilone core assembly | Source-annotated assembly participation, not independently assayed catalysis. No direct protein-to-final-product reaction, exact intermediate, stoichiometry, substrate specificity, physical complex or complete reaction order is asserted. GROUNDED denotes identifier identity, not experimental validation. SMP44 references are not interchangeable with So0157-2 proteins, whose epo gene names differ. | https://www.ebi.ac.uk/ena/browser/view/AF217189.1 |
| SMP44 epothilone core assembly | contributes_to_biosynthesis_of | epothilone B | The assembly process is shared by epothilone congeners, not B-specific. It does not alone perform final epoxidation; the existing EpoK graph separately records that step. No edge crosses graph-local node identifiers. Source-annotated assembly participation, not independently assayed catalysis. No direct protein-to-final-product reaction, exact intermediate, stoichiometry, substrate specificity, physical complex or complete reaction order is asserted. GROUNDED denotes identifier identity, not experimental validation. SMP44 references are not interchangeable with So0157-2 proteins, whose epo gene names differ. | DOI:10.1126/science.287.5453.640 |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — biosynthesis 8 nodes, 7 edges
6 exact So ce90 references with proposed source-annotated biosynthetic participation. Gene names follow this native deposit, not SMP44. Native PKS/NRPS annotations do not establish exact module reactions. UniProt automated thailandamide and fatty-acid annotations are not adopted. Only six new core references are included; the existing Q9KIZ4 EpoK graph is not duplicated or rewritten. The primary 2000 paper was inaccessible; citation metadata is not treated as inspected experimental evidence. Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| EpoA (So ce90 reference) | is_proposed_biosynthetic_participant_in | So ce90 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/AF210843.1 |
| EpoP (So ce90 reference) | is_proposed_biosynthetic_participant_in | So ce90 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/AF210843.1 |
| EpoB (So ce90 reference) | is_proposed_biosynthetic_participant_in | So ce90 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/AF210843.1 |
| EpoC (So ce90 reference) | is_proposed_biosynthetic_participant_in | So ce90 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/AF210843.1 |
| EpoD (So ce90 reference) | is_proposed_biosynthetic_participant_in | So ce90 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/AF210843.1 |
| EpoE (So ce90 reference) | is_proposed_biosynthetic_participant_in | So ce90 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/AF210843.1 |
| So ce90 proposed epothilone biosynthesis | is_source_associated_with_biosynthesis_of | epothilone B | Source-level cluster attribution shared across epothilone congeners, not proof of B-specificity or sufficiency of these proteins. Gene names follow this native deposit, not SMP44. Native PKS/NRPS annotations do not establish exact module reactions. UniProt automated thailandamide and fatty-acid annotations are not adopted. Only six new core references are included; the existing Q9KIZ4 EpoK graph is not duplicated or rewritten. The primary 2000 paper was inaccessible; citation metadata is not treated as inspected experimental evidence. Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://mibig.secondarymetabolites.org/repository/BGC0000988.5/annotations.json |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — biosynthesis 9 nodes, 8 edges
7 exact So0157-2 references with proposed source-annotated biosynthetic participation. Gene names follow this native deposit, not SMP44. Native PKS/NRPS annotations do not establish exact module reactions. UniProt automated thailandamide and fatty-acid annotations are not adopted. EpoF/D3G7A8 is a generic P450 with homology-level existence, not an experimentally established epothilone D epoxidase. The inspected 2013 abstract concerns promoters, not individual synthase assays; full text was inaccessible. Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| EpoA (So0157-2 reference) | is_proposed_biosynthetic_participant_in | So0157-2 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/EU414841.1 |
| EpoP (So0157-2 reference) | is_proposed_biosynthetic_participant_in | So0157-2 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/EU414841.1 |
| EpoB (So0157-2 reference) | is_proposed_biosynthetic_participant_in | So0157-2 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/EU414841.1 |
| EpoC (So0157-2 reference) | is_proposed_biosynthetic_participant_in | So0157-2 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/EU414841.1 |
| EpoD (So0157-2 reference) | is_proposed_biosynthetic_participant_in | So0157-2 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/EU414841.1 |
| EpoE (So0157-2 reference) | is_proposed_biosynthetic_participant_in | So0157-2 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/EU414841.1 |
| EpoF (So0157-2 reference) | is_proposed_biosynthetic_participant_in | So0157-2 proposed epothilone biosynthesis | Native annotation is only cytochrome P450/EPOS F; no epothilone D-to-B epoxidation is imported from EpoK. Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/EU414841.1 |
| So0157-2 proposed epothilone biosynthesis | is_source_associated_with_biosynthesis_of | epothilone B | Source-level cluster attribution shared across epothilone congeners, not proof of B-specificity or sufficiency of these proteins. Gene names follow this native deposit, not SMP44. Native PKS/NRPS annotations do not establish exact module reactions. UniProt automated thailandamide and fatty-acid annotations are not adopted. EpoF/D3G7A8 is a generic P450 with homology-level existence, not an experimentally established epothilone D epoxidase. The inspected 2013 abstract concerns promoters, not individual synthase assays; full text was inaccessible. Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://mibig.secondarymetabolites.org/repository/BGC0000989.3/annotations.json |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — biosynthesis 9 nodes, 8 edges
7 exact KYC3013 references with proposed source-annotated biosynthetic participation. Gene names follow this native deposit, not SMP44. Native PKS/NRPS annotations do not establish exact module reactions. UniProt automated thailandamide and fatty-acid annotations are not adopted. All seven historical UniProt entries D2X8Z3-D2X8Z9 are deleted; versioned GenPept references are used instead. The native record has a direct-submission reference. The legacy MIBiG paper concerns So ce90 and is not KYC3013 experimental proof. Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| EpoA (KYC3013 reference) | is_proposed_biosynthetic_participant_in | KYC3013 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/GU063811.1 |
| EpoB (KYC3013 reference) | is_proposed_biosynthetic_participant_in | KYC3013 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/GU063811.1 |
| EpoC (KYC3013 reference) | is_proposed_biosynthetic_participant_in | KYC3013 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/GU063811.1 |
| EpoD (KYC3013 reference) | is_proposed_biosynthetic_participant_in | KYC3013 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/GU063811.1 |
| EpoE (KYC3013 reference) | is_proposed_biosynthetic_participant_in | KYC3013 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/GU063811.1 |
| EpoF (KYC3013 reference) | is_proposed_biosynthetic_participant_in | KYC3013 proposed epothilone biosynthesis | Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/GU063811.1 |
| EpoK (KYC3013 reference) | is_proposed_biosynthetic_participant_in | KYC3013 proposed epothilone biosynthesis | P450 epoxidase is depositor wording only; no measured D-to-B reaction, substrate or EpoK assay is transferred. Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://www.ebi.ac.uk/ena/browser/view/GU063811.1 |
| KYC3013 proposed epothilone biosynthesis | is_source_associated_with_biosynthesis_of | epothilone B | Source-level cluster attribution shared across epothilone congeners, not proof of B-specificity or sufficiency of these proteins. Gene names follow this native deposit, not SMP44. Native PKS/NRPS annotations do not establish exact module reactions. UniProt automated thailandamide and fatty-acid annotations are not adopted. All seven historical UniProt entries D2X8Z3-D2X8Z9 are deleted; versioned GenPept references are used instead. The native record has a direct-submission reference. The legacy MIBiG paper concerns So ce90 and is not KYC3013 experimental proof. Proposed biosynthetic participation from native-locus annotations and the database cluster link, not an independently assayed catalytic function. No exact substrate, intermediate, reaction order, stoichiometry, physical complex or protein-to-final-product reaction is asserted. GROUNDED denotes reference identity, not experimental validation. Strain-specific gene names and sequences are not interchangeable with SMP44 or other strains; no assay construct or stock equivalence is claimed. | https://mibig.secondarymetabolites.org/repository/BGC0000990.3/annotations.json |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — bioactivity 4 nodes, 3 edges
Deposited epothilone-B contact and tubulin model-subunit references in 9PND version 1.2 (revised 2025-12-17), an in situ mouse thalamic-axon microtubule reconstruction. The graph records model geometry and assembly membership, not an isoform-specific drug assay. The local assembly node is the deposited segment, not a claim that a native microtubule is a tetramer. The primary paper DOI:10.1038/s41586-025-09654-z was inaccessible; only its abstract on the PDB page was inspected, and no downstream causal result is imported. These are deposited model references, not proof of uniform native isoforms, processing or post-translational modifications. No isoform-selective binding, affinity, potency, precise hydrogen bond, downstream regeneration or clinical effect is asserted. GROUNDED denotes reference identity, not an independent functional assay.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| epothilone B | has_deposited_model_contact_with | Tubb3 (9PND model reference) | Contact is scoped to the 9PND deposited beta-tubulin model. The deposited 3.19-Angstrom resolution is not a ligand-specific fit estimate. The official 2026-03-06 validation report gives EPB instances B503/D503 two/three bond-angle outliers and 18 of 51 analyzed torsions flagged in each; no EPB bond-length or chiral outliers are reported. Its unmasked half-map FSC 0.143 estimate is 5.81 Angstrom, a different calculation from the reported resolution. These caveats preclude treating model proximity as validated precise chemistry. No independent map refitting or experimental reanalysis was performed. These are deposited model references, not proof of uniform native isoforms, processing or post-translational modifications. No isoform-selective binding, affinity, potency, precise hydrogen bond, downstream regeneration or clinical effect is asserted. GROUNDED denotes reference identity, not an independent functional assay. | https://www.rcsb.org/structure/9PND |
| Tubb3 (9PND model reference) | is_modeled_subunit_of | 9PND modeled microtubule segment | Entity 1 model chains A/B (author B/D) contain coordinates for reference residues 1-428; residues 429-450 are unmodeled. This does not establish that every native beta subunit is Tubb3 or that the drug is beta-3 selective. These are deposited model references, not proof of uniform native isoforms, processing or post-translational modifications. No isoform-selective binding, affinity, potency, precise hydrogen bond, downstream regeneration or clinical effect is asserted. GROUNDED denotes reference identity, not an independent functional assay. | https://www.rcsb.org/structure/9PND |
| Tuba1a (9PND model reference) | is_modeled_subunit_of | 9PND modeled microtubule segment | Entity 2 model chains C/D (author A/C) contain coordinates for reference residues 1-439; residues 440-451 are unmodeled. The deposited name says detyrosinated, while the full declared reference ends Y451. The absent tail cannot settle native processing; this node denotes the canonical model reference, not a tyrosinated or detyrosinated proteoform. No alpha direct-contact edge is asserted. These are deposited model references, not proof of uniform native isoforms, processing or post-translational modifications. No isoform-selective binding, affinity, potency, precise hydrogen bond, downstream regeneration or clinical effect is asserted. GROUNDED denotes reference identity, not an independent functional assay. | https://www.rcsb.org/structure/9PND |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — bioactivity 5 nodes, 4 edges
A modeled S. pombe microtubule-Cut7 segment, not a native three-subunit microtubule. 6S8M version 1.4 (2025-10-01) supersedes 5MLV as alternative modeling of the same data, not an independent experiment. All three gene-source and expression-host tables name S. pombe NCBITaxon:4896 with unspecified strains; UniProt references name strain 972, NCBITaxon:284812, which does not establish experimental-stock equivalence. The primary paper DOI:10.1016/j.jmb.2019.01.011 was inaccessible; only its abstract on the PDB page was inspected. No primary assay result is imported. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| epothilone B | has_deposited_model_contact_with | nda3 (6S8M model reference) | The reported 4.5-Angstrom EM resolution is not ligand-specific. The official 2026-03-06 report flags four EPB bond lengths, 18 angles, 19 of 51 torsions and one of three analyzed rings, with no chirality outliers. The instance API gives Q_score 0.428, completeness 1.0 and 58 intermolecular clashes; the PDF short-contact count 35 is a differently defined metric. Overall model Q-score 0.358 and atom inclusion 0.677 at contour 0.0811 are not ligand-specific. These limitations preclude interpreting proximity as validated precise chemistry. No independent map refitting occurred. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets. | https://www.rcsb.org/structure/6S8M |
| cut7 (6S8M model reference) | is_modeled_component_of | 6S8M deposited microtubule-Cut7 segment | The 438-aa construct is GIDPFT plus canonical residues 1-432 of 1085-aa Cut7. The six leading residues are deposited expression tags. Model label chain A (author K) covers declared positions 74-302 and 324-438, corresponding to canonical 68-296 and 318-432. Author numbers are declared positions plus 27. This is neither full-length Cut7 nor evidence that Cut7 directly contacts EPB. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets. | https://www.rcsb.org/structure/6S8M |
| nda3 (6S8M model reference) | is_modeled_component_of | 6S8M deposited microtubule-Cut7 segment | The full declared 448-aa sequence matches nda3. Model chain B covers positions 2-430; position 1 and 431-448 are unmodeled, not demonstrated deletions. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets. | https://www.rcsb.org/structure/6S8M |
| nda2 (6S8M model reference) | is_modeled_component_of | 6S8M deposited microtubule-Cut7 segment | The full declared 455-aa sequence matches nda2. Model label chain C (author A) covers 1-36 and 50-442; 37-49 and 443-455 are unmodeled. No alpha-tubulin drug-contact edge is asserted. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets. | https://www.rcsb.org/structure/6S8M |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — bioactivity 6 nodes, 5 edges
A deposited mixed-species tubulin-partner crystallization complex, not a native multispecies assembly. 7DAE version 1.1 (2023-11-29) models native-source porcine tubulins (taxon 9823), an engineered mouse Stmn4 fragment (taxon 10090), and an engineered chicken TTL construct (taxon 9031); the latter two are expressed in E. coli (taxon 562) according to the deposit. Strains are unspecified. Alternate conformers and partial protein-atom occupancies are retained. The primary paper DOI:10.1016/j.bbrc.2020.11.082 was inaccessible; only its abstract on the PDB page was inspected. No primary assay result is imported. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| epothilone B | has_deposited_model_contact_with | LOC100624785 (7DAE model reference) | The deposited X-ray resolution is 2.394 Angstrom. The official 2026-03-05 report flags 15 EPB bond lengths, 17 angles and six of 51 torsions, with no chiral or ring outliers. Instance metrics RSCC 0.908, RSR 0.129, completeness 1.0 and six intermolecular clashes coexist with those geometry warnings. Density illustrations are not independent refinement or an affinity measurement; no precise hydrogen-bond chemistry is adjudicated. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets. | https://www.rcsb.org/structure/7DAE |
| TUBA1B (7DAE model reference) | is_modeled_component_of | 7DAE deposited tubulin-partner complex | The full declared 451-aa sequence matches TUBA1B. Model chains A/C cover 1-439/1-440, leaving their remaining C-terminal residues unmodeled. Native proteoform processing is not resolved. No alpha-tubulin drug-contact edge is asserted. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets. | https://www.rcsb.org/structure/7DAE |
| LOC100624785 (7DAE model reference) | is_modeled_component_of | 7DAE deposited tubulin-partner complex | The full declared 445-aa sequence matches LOC100624785. Model B covers 1-276 and 280-430; model D covers 2-431. Unmodeled intervals do not establish sequence deletions. Some author residue numbers differ from declared/reference positions. Only model D has the deposited EPB instance; neither every beta copy nor every native beta isoform is asserted to bind the drug. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets. | https://www.rcsb.org/structure/7DAE |
| Stmn4 (7DAE model reference) | is_modeled_component_of | 7DAE deposited tubulin-partner complex | The 143-aa construct is MA plus canonical Stmn4 residues 49-189. The deposit annotates the leading M as initiating methionine and A as expression tag. Model E covers declared positions 4-26 and 42-142, corresponding to canonical 50-72 and 88-188. This truncated crystallization partner is not a demonstrated EPB target or a full-length native Stmn4 assay. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets. | https://www.rcsb.org/structure/7DAE |
| TTL (7DAE model reference) | is_modeled_component_of | 7DAE deposited tubulin-partner complex | The 384-aa construct is the exact 378-aa NP_001186321.1 reference plus six terminal histidine expression tags. Model F covers declared positions 1-101,125-152,158-363 and 372-384, including the tag. Unmodeled loops do not establish sequence deletions. TTL is a modeled crystallization partner, not a demonstrated EPB target or a native multispecies subunit. GROUNDED identifies the deposited model reference, not an independently assayed native protein. No native isoform homogeneity, stock equivalence, processing state, affinity, potency, precise hydrogen bond, drug-induced assembly or downstream effect is asserted. Other modeled partners are not asserted to be drug targets. | https://www.rcsb.org/structure/7DAE |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Bioactivities 25
Entries preserve source qualifiers, targets and evidence. Repeated assay names or values are not independent replications; inspect source detail for differences.
| Assay | Result | Target enzyme | Source detail |
|---|---|---|---|
| A quantitative high throughput screen for small molecules that induce DNA re-replication in SW480 colon adenocarcinoma cells. | OTHER 3.3498 uM; NOT_DETERMINED | Not recorded | pubchem.aid:624297
|
| BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML: AML-191 cell line | OTHER 0.0105 uM; ACTIVE | Not recorded | pubchem.aid:2202236
|
| BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML: AML-194 cell line | OTHER 0.0118 uM; ACTIVE | Not recorded | pubchem.aid:2202237
|
| BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML: HNT-34 cell line | OTHER 0.0083 uM; ACTIVE | Not recorded | pubchem.aid:2202234
|
| BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML: MV-4-11 cell line | OTHER 0.0093 uM; ACTIVE | Not recorded | pubchem.aid:2202233
|
| BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML: OCI-AML3 cell line | OTHER 0.0059 uM; ACTIVE | Not recorded | pubchem.aid:2202232
|
| BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML: SET-2 cell line | OTHER 0.0186 uM; ACTIVE | Not recorded | pubchem.aid:2202231
|
| BET inhibitor-based combinations targeting novel dependencies in MECOM-rearranged (r) AML: UCSD-AML1 cell line | OTHER 0.0059 uM; ACTIVE | Not recorded | pubchem.aid:2202235
|
| Cellular viability qHTS for adrenocortical cancer (ACC) cell line NCI-H295R | OTHER 0.0282 uM; ACTIVE | Not recorded | pubchem.aid:1963990
|
| Cellular viability qHTS for adrenocortical cancer (ACC) cell line SW-13 | OTHER 0.0282 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1963989
|
| Cellular viability qHTS for anaplastic thyroid cancer (ATC) cell line 8505C | OTHER 0.039 uM; ACTIVE | Not recorded | pubchem.aid:2202553
|
| Cellular viability qHTS for anaplastic thyroid cancer (ATC) cell line THJ-11T | OTHER 0.0693 uM; NOT_DETERMINED | Not recorded | pubchem.aid:2202552
|
| Cellular viability qHTS for anaplastic thyroid cancer (ATC) cell line THJ-16T | OTHER 0.0219 uM; ACTIVE | Not recorded | pubchem.aid:2202551
|
| Confirmatory qHTS to identify inhibitors of SARS-CoV-2 cell entry | OTHER 0.0541 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1645844
|
| Human pregnane X receptor (PXR) activation by small molecules, qHTS assay | OTHER 7.9433 uM; ACTIVE | Not recorded | pubchem.aid:1346985
|
| P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen | OTHER 0.0366 uM; ACTIVE | Not recorded | PMID:31515284
|
| Primary qHTS for delayed death inhibitors of the malarial parasite plastid, 48 hour incubation | OTHER 0.0013 uM; ACTIVE | Not recorded | pubchem.aid:504832
|
| Primary qHTS for delayed death inhibitors of the malarial parasite plastid, 96 hour incubation | OTHER 0.0013 uM; NOT_DETERMINED | Not recorded | pubchem.aid:504834
|
| Primary qHTS for inhibitors of nuclear receptor binding SET domain protein 2 (NSD2) in an RCH-ACV wild type WT cells (2C) | OTHER 0.0059 uM; ACTIVE | Not recorded | pubchem.aid:1645877
|
| Primary qHTS for inhibitors of nuclear receptor binding SET domain protein 2 (NSD2) in an RCH-ACV wild type WT cells (2C) | OTHER 0.0059 uM; ACTIVE | UniProtKB:O96028 | pubchem.aid:1645877
|
| Primary qHTS for inhibitors of nuclear receptor binding SET domain protein 2 (NSD2) in an isogenic RCH-ACV NSD2 p.E1099K mutant (9B) | OTHER 0.0066 uM; ACTIVE | Not recorded | pubchem.aid:1645876
|
| Primary qHTS for inhibitors of nuclear receptor binding SET domain protein 2 (NSD2) in an isogenic RCH-ACV NSD2 p.E1099K mutant (9B) | OTHER 0.0066 uM; ACTIVE | UniProtKB:O96028 | pubchem.aid:1645876
|
| Rat pregnane X receptor (rPXR) activation by small molecules, qHTS assay | OTHER 10 uM; ACTIVE | Not recorded | pubchem.aid:1346983
|
| S16 Schwann cell PMP22 intronic element beta-lactamase assay | OTHER 0.0112 uM; NOT_DETERMINED | Not recorded | pubchem.aid:624044
|
| S16 Schwann cell PMP22 intronic element firefly luciferase assay | OTHER 0.0573 uM; ACTIVE | Not recorded | pubchem.aid:624032
|
Explore across X-Mech
AntibioticMech (epothilone B) ↗
MediaIngredientMech (CHEBI:31550) ↗
TaxonMech: Sorangium cellulosum (NCBITaxon:56) ↗
TaxonMech: Sorangium cellulosum So0157-2 (NCBITaxon:1254432) ↗
TaxonMech: Sorangium cellulosum (NCBITaxon:56) ↗
TaxonMech: Sorangium cellulosum (NCBITaxon:56) ↗
PathwayMech (mibig:BGC0000988) ↗
PathwayMech (mibig:BGC0000989) ↗
PathwayMech (mibig:BGC0000990) ↗
Open questions 1
shared-structure — This structure is reported by more than one MIBiG entry: BGC0000988, BGC0000989, BGC0000990, BGC0000991. Confirm they describe the same compound rather than an upstream cross-reference error.
Provenance
| Source concept | Source | Version |
|---|---|---|
| BGC0000988 | MIBIG | 5 |
| BGC0000989 | MIBIG | 3 |
| BGC0000990 | MIBIG | 3 |
| BGC0000991 | MIBIG | 4 |
| CHEBI:31550 | CHEBI | 3-star |
This page is generated from data/natural_products/unclassified/epothilone-b.yaml, which is generated from the committed inventories. Neither is edited by hand.