griseofulvin
naturalproductmech:mibig-e59592cca0 MINTED SEEDED cytotoxic
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REVIEWED records curator sign-off on identity, structure, filing class and producer claims; DEPRECATED retains a superseded or out-of-scope record.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.
Structure
| Standard InChIKey | DDUHZTYCFQRHIY-OEWHWVHBSA-N |
|---|---|
| SMILES | COC1=CC(OC)=C(Cl)C2=C1C(=O)C1(O2)[C@H](C)CC(=O)C=C1OC |
| Stereochemistry | undefined stereocentres — the InChIKey does not distinguish this compound from its stereoisomers |
| Cross-references | pubchem:441140, npatlas:NPA02483 |
Filing pathway
Polyketides — 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 pks, from MIBiG.
Producer organisms 1
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 |
|---|---|---|---|
| Penicillium aethiopicum NCBITaxon:36650 |
BGC_CHARACTERIZED | mibig:BGC0000070 | DOI:10.1021/cb400541z |
Occurrences 1
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 |
|---|---|---|
| Penicillium griseum NCBITaxon:1131486 |
LOTUS | DOI:10.1042/BJ0330240 |
Biosynthetic gene clusters 1
| Accession | Host | Locus evidence | Genome |
|---|---|---|---|
| mibig:BGC0000070 | Penicillium aethiopicum NCBITaxon:36650 |
CLUSTER_DEMONSTRATED | genbank:GU574478.1 |
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 | GsfA non-reducing polyketide synthase UniProtKB:D7PI15 |
RHEA:73915 | CHEBI:57288 + CHEBI:57384 → CHEBI:193062 | DOI:10.1021/cb400541z |
| 2 | GsfB O-methyltransferase UniProtKB:D7PI16 |
RHEA:73923 | CHEBI:193062 → CHEBI:193064 | DOI:10.1021/cb400541z |
| 3 | GsfC O-methyltransferase UniProtKB:D7PI17 |
RHEA:73927 | CHEBI:193064 → CHEBI:193065 | DOI:10.1021/cb400541z |
| 4 | GsfI flavin-dependent halogenase UniProtKB:D7PI14 |
RHEA:73931 | CHEBI:193065 → CHEBI:193066 | DOI:10.1021/cb400541z |
| 5 | GsfF cytochrome P450 monooxygenase UniProtKB:D7PI20 |
RHEA:73935 | CHEBI:193066 → CHEBI:193067 | DOI:10.1021/cb400541z |
| 6 | GsfD O-methyltransferase UniProtKB:D7PI18 |
RHEA:73939 | CHEBI:193067 → CHEBI:81999 | DOI:10.1021/cb400541z |
| 7 | GsfE short-chain dehydrogenase UniProtKB:D7PI19 |
RHEA:73943 | CHEBI:81999 → naturalproductmech:mibig-e59592cca0 | DOI:10.1021/cb400541z |
Step 1: GsfA is proposed to form the heptaketide benzophenone from acetyl-CoA and six malonyl-CoA units; Rhea captures this non-reducing polyketide synthase reaction as RHEA:73915.
Step 2: GsfB methylates the GsfA benzophenone product at 3-OH to yield griseophenone D, the immediate substrate for GsfC; Rhea captures the SAM-dependent methyltransferase reaction as RHEA:73923.
Step 3: GsfC methylates griseophenone D at 9-OH to yield griseophenone C, the immediate substrate for GsfI; Rhea captures the SAM-dependent methyltransferase reaction as RHEA:73927.
Step 4: GsfI chlorinates griseophenone C at C13 to form griseophenone B immediately upstream of GsfF-catalyzed grisan scaffold formation; Rhea captures the reduced-flavin chlorination as RHEA:73931.
Step 5: GsfF performs the late oxidative phenolic coupling that converts griseophenone B into the grisan scaffold of desmethyl-dehydrogriseofulvin during griseofulvin biosynthesis.
Step 6: GsfD is proposed to methylate desmethyl-dehydrogriseofulvin at 5-OH to yield dehydrogriseofulvin; Rhea maps the SAM-dependent GsfD O-methyltransferase to RHEA:73939.
Step 7: GsfE stereospecifically reduces dehydrogriseofulvin to griseofulvin with NADPH; Rhea maps this final reductase reaction to RHEA:73943.
Mechanism & Biosynthesis Overview
Causal graph — biosynthesis 4 nodes, 3 edges
Partial P. aethiopicum griseofulvin biosynthesis graph for proposed GsfA-catalyzed heptaketide benzophenone formation.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| acetyl-CoA(4-) | is extended by | GsfA non-reducing polyketide synthase | GsfA is proposed to prime the griseofulvin heptaketide backbone with acetyl-CoA before extension by malonyl-CoA. | DOI:10.1021/cb400541z |
| malonyl-CoA(5-) | is condensed by | GsfA non-reducing polyketide synthase | GsfA sequentially condenses six malonyl-CoA units while building the benzophenone precursor. | DOI:10.1021/cb400541z |
| GsfA non-reducing polyketide synthase | forms | 2-(2,4-dihydroxy-6-oxidobenzoyl)-5-hydroxy-3-methylbenzenolate | The labile GsfA benzophenone product is inferred to be the immediate upstream substrate for GsfB; when it is not captured by GsfB, it can spontaneously dehydrate to the off-pathway shunt product norlichexanthone. | DOI:10.1021/cb400541z |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — biosynthesis 3 nodes, 2 edges
Partial P. aethiopicum griseofulvin biosynthesis graph for GsfB-catalyzed 3-O-methylation.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| 2-(2,4-dihydroxy-6-oxidobenzoyl)-5-hydroxy-3-methylbenzenolate | is methylated by | GsfB O-methyltransferase | GsfB is the 3-OH O-methyltransferase that installs the methyl group yielding griseophenone D. | DOI:10.1021/cb400541z |
| GsfB O-methyltransferase | forms | griseophenone D | The SAM-dependent GsfB reaction converts the GsfA benzophenone product into griseophenone D, placing GsfB immediately upstream of GsfC-catalyzed methylation. | DOI:10.1021/cb400541z |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — biosynthesis 3 nodes, 2 edges
Partial P. aethiopicum griseofulvin biosynthesis graph for GsfC-catalyzed griseophenone D 9-O-methylation.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| griseophenone D | is methylated by | GsfC O-methyltransferase | GsfC is the 9-OH O-methyltransferase that installs the methyl group yielding griseophenone C. | DOI:10.1021/cb400541z |
| GsfC O-methyltransferase | forms | griseophenone C | The SAM-dependent GsfC reaction converts griseophenone D into griseophenone C, placing GsfC immediately upstream of GsfI-catalyzed halogenation. | DOI:10.1021/cb400541z |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — biosynthesis 3 nodes, 2 edges
Partial P. aethiopicum griseofulvin biosynthesis graph for GsfI-catalyzed griseophenone C chlorination.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| griseophenone C | is chlorinated by | GsfI flavin-dependent halogenase | GsfI catalyzes chlorination of griseophenone C to produce griseophenone B; Cacho et al. used SsuE as the NADPH-dependent flavin reductase in the in vitro reconstitution. | DOI:10.1021/cb400541z |
| GsfI flavin-dependent halogenase | forms | griseophenone B | The chlorinated product is compound 11 in the primary paper and is curated as griseophenone B in ChEBI and Rhea. | DOI:10.1021/cb400541z |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — biosynthesis 3 nodes, 2 edges
Partial P. aethiopicum griseofulvin biosynthesis graph for GsfF-catalyzed grisan scaffold formation.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| griseophenone B | is oxidatively coupled by | GsfF cytochrome P450 monooxygenase | GsfF catalyzes oxidative coupling of the orcinol and phloroglucinol rings in griseophenone B. | DOI:10.1021/cb400541z |
| GsfF cytochrome P450 monooxygenase | forms | desmethyl-dehydrogriseofulvin | The spirocyclic product is compound 14 in the primary paper and is curated as desmethyl-dehydrogriseofulvin in ChEBI and Rhea. | DOI:10.1021/cb400541z |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — biosynthesis 3 nodes, 2 edges
Partial P. aethiopicum griseofulvin biosynthesis graph for proposed GsfD-catalyzed 5-O-methylation.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| desmethyl-dehydrogriseofulvin | is methylated by | GsfD O-methyltransferase | GsfD is proposed to methylate the 5-OH of desmethyl-dehydrogriseofulvin. | DOI:10.1021/cb400541z |
| GsfD O-methyltransferase | forms | dehydrogriseofulvin | The proposed SAM-dependent GsfD reaction converts desmethyl-dehydrogriseofulvin to dehydrogriseofulvin before GsfE-catalyzed reduction. | DOI:10.1021/cb400541z |
Every edge carries its own citation; an uncited edge is refused by the corpus tests.
Causal graph — biosynthesis 3 nodes, 2 edges
Partial P. aethiopicum griseofulvin biosynthesis graph for GsfE-catalyzed final reduction.
| Subject | Predicate | Object | Notes | Evidence |
|---|---|---|---|---|
| dehydrogriseofulvin | is reduced by | GsfE short-chain dehydrogenase | GsfE reduces dehydrogriseofulvin with NADPH in the final step of griseofulvin biosynthesis. | DOI:10.1021/cb400541z |
| GsfE short-chain dehydrogenase | forms | griseofulvin | His-tagged GsfE converted dehydrogriseofulvin, compound 18, to griseofulvin, compound 1, in vitro. | DOI:10.1021/cb400541z |
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 |
|---|---|---|---|
| 5-hydroxytryptamine receptor 2A (HTR2A) small molecule antagonists, cell-based qHTS assay | OTHER 23.4556 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1963586
|
| 5-hydroxytryptamine receptor 2A (HTR2A) small molecule antagonists, cell-based qHTS assay | OTHER 23.4556 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1963586
|
| 5-hydroxytryptamine receptor 2A (HTR2A) small molecule antagonists, cell-based qHTS assay | OTHER 23.0537 uM; INACTIVE | Not recorded | pubchem.aid:1963586
|
| 5-hydroxytryptamine receptor 2A (HTR2A) small molecule antagonists, cell-based qHTS assay | OTHER 23.0537 uM; INACTIVE | Not recorded | pubchem.aid:1963586
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HEK293 cells - 0 hour | OTHER 30.6312 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1224869
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HEK293 cells - 16 hour | OTHER 30.6312 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1224888
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HEK293 cells - 24 hour | OTHER 34.3687 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1224875
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HEK293 cells - 32 hour | OTHER 38.5624 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1224881
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HEK293 cells - 40 hour | OTHER 38.5624 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1224871
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HEK293 cells - 8 hour | OTHER 24.3312 uM; ACTIVE | Not recorded | pubchem.aid:1224884
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HepG2 cells - 16 hour | OTHER 24.5412 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1224876
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HepG2 cells - 24 hour | OTHER 38.5624 uM; ACTIVE | Not recorded | pubchem.aid:1224878
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HepG2 cells - 24 hour | OTHER 21.8724 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1224878
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HepG2 cells - 32 hour | OTHER 34.3687 uM; ACTIVE | Not recorded | pubchem.aid:1224883
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HepG2 cells - 32 hour | OTHER 21.8724 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1224883
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HepG2 cells - 32 hour | OTHER 26.8325 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1224883
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HepG2 cells - 40 hour | OTHER 24.3312 uM; ACTIVE | Not recorded | pubchem.aid:1224879
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HepG2 cells - 40 hour | OTHER 21.8724 uM; ACTIVE | Not recorded | pubchem.aid:1224879
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HepG2 cells - 40 hour | OTHER 26.8325 uM; ACTIVE | Not recorded | pubchem.aid:1224879
|
| A CellTox Green Cytotoxicity Assay to monitor cytotoxicity in HepG2 cells - 8 hour | OTHER 48.9662 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1224890
|
| A quantitative high throughput screen for small molecules that induce DNA re-replication in MCF 10a normal breast cells. | OTHER 21.136 uM; NOT_DETERMINED | Not recorded | pubchem.aid:624296
|
| A quantitative high throughput screen for small molecules that induce DNA re-replication in MCF 10a normal breast cells. | OTHER 6.5131 uM; NOT_DETERMINED | Not recorded | pubchem.aid:624296
|
| A quantitative high throughput screen for small molecules that induce DNA re-replication in SW480 colon adenocarcinoma cells. | OTHER 33.4983 uM; NOT_DETERMINED | Not recorded | pubchem.aid:624297
|
| A quantitative high throughput screen for small molecules that induce DNA re-replication in SW480 colon adenocarcinoma cells. | OTHER 22.3872 uM; NOT_DETERMINED | Not recorded | pubchem.aid:624297
|
| Caspase-3/7 induction in CHO-K1 cells by small molecules, qHTS cell viability counter screen | OTHER 42.8813 uM; NOT_DETERMINED | Not recorded | pubchem.aid:1346979
|
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Provenance
| Source concept | Source | Version |
|---|---|---|
| BGC0000070 | MIBIG | 5 |
This page is generated from data/natural_products/polyketides/griseofulvin.yaml, which is generated from the committed inventories. Neither is edited by hand.