leporin B

naturalproductmech:mibig-6752ae6cca MINTED SEEDED

Grounding review: No 3-star ChEBI entry shares this structure, so the record keeps a content-hashed identifier.

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REVIEWED records curator sign-off on identity, structure, filing class and producer claims; DEPRECATED retains a superseded or out-of-scope record.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	ZAWHOLMDNIHGEJ-FPYGCLRLSA-N
SMILES	CC(CCC1)C(C1C(/C=C/C)O2)C3=C2C(C4=CC=CC=C4)=CN(O)C3=O
Stereochemistry	undefined stereocentres — the InChIKey does not distinguish this compound from its stereoisomers

Filing pathway

Alkaloids — 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 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
Aspergillus flavus NRRL3357 NCBITaxon:332952	BGC_CHARACTERIZED	mibig:BGC0001445	PMID:26051490

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
Aspergillus flavus NCBITaxon:5059	LOTUS	DOI:10.1016/J.FGB.2015.05.010

Biosynthetic gene clusters 1

Accession	Host	Locus evidence	Genome
mibig:BGC0001445	Aspergillus flavus NRRL3357 NCBITaxon:332952	CLUSTER_DEMONSTRATED	genbank:EQ963479.1

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	Substrate → product	Evidence
1	LepF short-chain dehydrogenase/reductase UniProtKB:B8NJH0	ungrounded → ungrounded	DOI:10.1038/nature23882
2	LepI SAM-dependent pericyclase UniProtKB:B8NJH3	ungrounded → ungrounded	DOI:10.1038/nature23882
3	LepD cytochrome P450 monooxygenase UniProtKB:B8NJG8	ungrounded → naturalproductmech:mibig-6752ae6cca	DOI:10.1038/nature23882

Step 1: Primary-literature and MITE0000294-supported reduction of ketone 3 to alcohol 4 precursor for LepI by Aspergillus flavus NRRL 3357 LepF (UniProtKB:B8NJH0, EED49869.1, AFLA_066910 on EQ963479.1, BGC0001445.5, DOI:10.1038/nature23882). Synchronizes biosynthetic_pathway with the existing causal_graph without upgrading producer or locus evidence grades.

Step 2: Primary-literature and MITE0000316-supported stereoselective dehydration of alcohol 4 to (E)-o-quinone methide 5 and hetero-Diels-Alder cyclization to leporin C by Aspergillus flavus NRRL 3357 LepI (UniProtKB:B8NJH3, EED49872.1, AFLA_066940 on EQ963479.1, BGC0001445.5, DOI:10.1038/nature23882). Synchronizes biosynthetic_pathway with the existing causal_graph without upgrading producer or locus evidence grades.

Step 3: Primary-literature and MITE0000321-supported N-hydroxylation of leporin C to leporin B (naturalproductmech:mibig-6752ae6cca) by Aspergillus flavus NRRL 3357 LepD (UniProtKB:B8NJG8, EED49867.1, AFLA_066890 on EQ963479.1, BGC0001445.5, DOI:10.1038/nature23882). Synchronizes biosynthetic_pathway with the existing causal_graph without upgrading producer or locus evidence grades.

Mechanism & Biosynthesis Overview

Causal graph — biosynthesis 3 nodes, 2 edges

Aspergillus flavus LepD-catalyzed N-hydroxylation of leporin C to leporin B.

Subject	Predicate	Object	Notes	Evidence
leporin C	is N-hydroxylated by	LepD cytochrome P450 monooxygenase	LepD adds the N-hydroxy group that distinguishes the final hydroxamic-acid product leporin B from the 2-pyridone precursor leporin C.	DOI:10.1038/nature23882 https://mite.lisc.univie.ac.at/repository/MITE0000321 https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk https://www.uniprot.org/uniprotkb/B8NJG8 https://www.ncbi.nlm.nih.gov/protein/EED49867.1 reference DOI:10.1038/nature23882 evidence type PRIMARY_EXPERIMENT snippet Further addition of the P450 lepD yielded the final product 1, thereby completing heterologous pathway reconstitution. notes Ohashi et al. heterologously reconstituted leporin B biosynthesis in Aspergillus nidulans; after LepA/LepG/LepH/LepF/LepI formed leporin C as the desired pyran product, further addition of LepD yielded leporin B. reference https://mite.lisc.univie.ac.at/repository/MITE0000321 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MITE0000321 is active and links LepD to UniProtKB:B8NJG8, GenPept EED49867.1, MIBiG BGC0001445 and the N-hydroxylation of leporin C to leporin B. reference https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0001445.5 places EED49867.1 in the active Aspergillus flavus NRRL3357 leporin B biosynthetic gene cluster as the AFLA_066890 cytochrome P450 locus. reference https://www.uniprot.org/uniprotkb/B8NJG8 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes Reviewed UniProtKB:B8NJG8 is the 508 aa Aspergillus flavus NRRL3357 cytochrome P450 monooxygenase LepD entry and cross-references EMBL EQ963479 protein EED49867.1. reference https://www.ncbi.nlm.nih.gov/protein/EED49867.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept EED49867.1 is the Aspergillus flavus NRRL3357 cytochrome P450 protein encoded by AFLA_066890 on EQ963479.1.
LepD cytochrome P450 monooxygenase	forms	leporin B	The heterologously reconstituted leporin pathway yielded leporin B after the P450 LepD was added downstream of the LepI-dependent leporin C step.	DOI:10.1038/nature23882 https://mite.lisc.univie.ac.at/repository/MITE0000321 https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk https://www.uniprot.org/uniprotkb/B8NJG8 https://www.ncbi.nlm.nih.gov/protein/EED49867.1 reference DOI:10.1038/nature23882 evidence type PRIMARY_EXPERIMENT snippet Further addition of the P450 lepD yielded the final product 1, thereby completing heterologous pathway reconstitution. notes Ohashi et al. heterologously reconstituted leporin B biosynthesis in Aspergillus nidulans; after LepA/LepG/LepH/LepF/LepI formed leporin C as the desired pyran product, further addition of LepD yielded leporin B. reference https://mite.lisc.univie.ac.at/repository/MITE0000321 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MITE0000321 is active and links LepD to UniProtKB:B8NJG8, GenPept EED49867.1, MIBiG BGC0001445 and the N-hydroxylation of leporin C to leporin B. reference https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0001445.5 places EED49867.1 in the active Aspergillus flavus NRRL3357 leporin B biosynthetic gene cluster as the AFLA_066890 cytochrome P450 locus. reference https://www.uniprot.org/uniprotkb/B8NJG8 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes Reviewed UniProtKB:B8NJG8 is the 508 aa Aspergillus flavus NRRL3357 cytochrome P450 monooxygenase LepD entry and cross-references EMBL EQ963479 protein EED49867.1. reference https://www.ncbi.nlm.nih.gov/protein/EED49867.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept EED49867.1 is the Aspergillus flavus NRRL3357 cytochrome P450 protein encoded by AFLA_066890 on EQ963479.1.

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

Causal graph — biosynthesis 4 nodes, 4 edges

Aspergillus flavus LepI-catalyzed stereoselective dehydration and hetero-Diels-Alder cyclization en route to leporin C.

Subject	Predicate	Object	Notes	Evidence
leporin alcohol 4	is stereoselectively dehydrated by	LepI SAM-dependent pericyclase	LepI dehydrates alcohol intermediate 4 to the (E)-5 o-quinone methide species that enters the pericyclic branch toward leporin C.	DOI:10.1038/nature23882 https://mite.lisc.univie.ac.at/repository/MITE0000316 https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk https://www.uniprot.org/uniprotkb/B8NJH3 https://www.ncbi.nlm.nih.gov/protein/EED49872.1 reference DOI:10.1038/nature23882 evidence type PRIMARY_EXPERIMENT snippet which requires stereoselective dehydration to yield (E)-5 and subsequent HDA reaction to 2 notes Ohashi et al. heterologously expressed lepI in Aspergillus nidulans and purified LepI from Escherichia coli; both assays supported LepI stereoselectively dehydrating alcohol 4 and controlling the pericyclic reactions that produce leporin C. reference https://mite.lisc.univie.ac.at/repository/MITE0000316 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MITE0000316 is active and links LepI to UniProtKB:B8NJH3, GenPept EED49872.1, MIBiG BGC0001445, stereoselective dehydration and a hetero-Diels-Alder reaction. reference https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0001445.5 places EED49872.1 in the active Aspergillus flavus NRRL3357 leporin B biosynthetic gene cluster as the AFLA_066940 O-methyltransferase locus. reference https://www.uniprot.org/uniprotkb/B8NJH3 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes Reviewed UniProtKB:B8NJH3 is the 387 aa Aspergillus flavus NRRL3357 O-methyltransferase LepI entry and cross-references EMBL EQ963479 protein EED49872.1. reference https://www.ncbi.nlm.nih.gov/protein/EED49872.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept EED49872.1 is the Aspergillus flavus NRRL3357 putative O-methyltransferase encoded by AFLA_066940 on EQ963479.1.
LepI SAM-dependent pericyclase	forms	(E)-o-quinone methide 5	MITE represents LepI stereoselective dehydration as the conversion of alcohol 4 into the (E)-o-quinone methide intermediate in the leporin pathway.	DOI:10.1038/nature23882 https://mite.lisc.univie.ac.at/repository/MITE0000316 https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk https://www.uniprot.org/uniprotkb/B8NJH3 https://www.ncbi.nlm.nih.gov/protein/EED49872.1 reference DOI:10.1038/nature23882 evidence type PRIMARY_EXPERIMENT snippet which requires stereoselective dehydration to yield (E)-5 and subsequent HDA reaction to 2 notes Ohashi et al. heterologously expressed lepI in Aspergillus nidulans and purified LepI from Escherichia coli; both assays supported LepI stereoselectively dehydrating alcohol 4 and controlling the pericyclic reactions that produce leporin C. reference https://mite.lisc.univie.ac.at/repository/MITE0000316 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MITE0000316 is active and links LepI to UniProtKB:B8NJH3, GenPept EED49872.1, MIBiG BGC0001445, stereoselective dehydration and a hetero-Diels-Alder reaction. reference https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0001445.5 places EED49872.1 in the active Aspergillus flavus NRRL3357 leporin B biosynthetic gene cluster as the AFLA_066940 O-methyltransferase locus. reference https://www.uniprot.org/uniprotkb/B8NJH3 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes Reviewed UniProtKB:B8NJH3 is the 387 aa Aspergillus flavus NRRL3357 O-methyltransferase LepI entry and cross-references EMBL EQ963479 protein EED49872.1. reference https://www.ncbi.nlm.nih.gov/protein/EED49872.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept EED49872.1 is the Aspergillus flavus NRRL3357 putative O-methyltransferase encoded by AFLA_066940 on EQ963479.1.
(E)-o-quinone methide 5	is cyclized by	LepI SAM-dependent pericyclase	The LepI-controlled hetero-Diels-Alder reaction converts the quinone methide intermediate into leporin C.	DOI:10.1038/nature23882 https://mite.lisc.univie.ac.at/repository/MITE0000316 https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk https://www.uniprot.org/uniprotkb/B8NJH3 https://www.ncbi.nlm.nih.gov/protein/EED49872.1 reference DOI:10.1038/nature23882 evidence type PRIMARY_EXPERIMENT snippet which requires stereoselective dehydration to yield (E)-5 and subsequent HDA reaction to 2 notes Ohashi et al. heterologously expressed lepI in Aspergillus nidulans and purified LepI from Escherichia coli; both assays supported LepI stereoselectively dehydrating alcohol 4 and controlling the pericyclic reactions that produce leporin C. reference https://mite.lisc.univie.ac.at/repository/MITE0000316 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MITE0000316 is active and links LepI to UniProtKB:B8NJH3, GenPept EED49872.1, MIBiG BGC0001445, stereoselective dehydration and a hetero-Diels-Alder reaction. reference https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0001445.5 places EED49872.1 in the active Aspergillus flavus NRRL3357 leporin B biosynthetic gene cluster as the AFLA_066940 O-methyltransferase locus. reference https://www.uniprot.org/uniprotkb/B8NJH3 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes Reviewed UniProtKB:B8NJH3 is the 387 aa Aspergillus flavus NRRL3357 O-methyltransferase LepI entry and cross-references EMBL EQ963479 protein EED49872.1. reference https://www.ncbi.nlm.nih.gov/protein/EED49872.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept EED49872.1 is the Aspergillus flavus NRRL3357 putative O-methyltransferase encoded by AFLA_066940 on EQ963479.1.
LepI SAM-dependent pericyclase	forms	leporin C	LepI forms leporin C, the direct LepD substrate for the final N-hydroxylation to leporin B.	DOI:10.1038/nature23882 https://mite.lisc.univie.ac.at/repository/MITE0000316 https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk https://www.uniprot.org/uniprotkb/B8NJH3 https://www.ncbi.nlm.nih.gov/protein/EED49872.1 reference DOI:10.1038/nature23882 evidence type PRIMARY_EXPERIMENT snippet which requires stereoselective dehydration to yield (E)-5 and subsequent HDA reaction to 2 notes Ohashi et al. heterologously expressed lepI in Aspergillus nidulans and purified LepI from Escherichia coli; both assays supported LepI stereoselectively dehydrating alcohol 4 and controlling the pericyclic reactions that produce leporin C. reference https://mite.lisc.univie.ac.at/repository/MITE0000316 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MITE0000316 is active and links LepI to UniProtKB:B8NJH3, GenPept EED49872.1, MIBiG BGC0001445, stereoselective dehydration and a hetero-Diels-Alder reaction. reference https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0001445.5 places EED49872.1 in the active Aspergillus flavus NRRL3357 leporin B biosynthetic gene cluster as the AFLA_066940 O-methyltransferase locus. reference https://www.uniprot.org/uniprotkb/B8NJH3 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes Reviewed UniProtKB:B8NJH3 is the 387 aa Aspergillus flavus NRRL3357 O-methyltransferase LepI entry and cross-references EMBL EQ963479 protein EED49872.1. reference https://www.ncbi.nlm.nih.gov/protein/EED49872.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept EED49872.1 is the Aspergillus flavus NRRL3357 putative O-methyltransferase encoded by AFLA_066940 on EQ963479.1.

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

Causal graph — biosynthesis 3 nodes, 2 edges

Aspergillus flavus LepF-catalyzed reduction of ketone 3 to leporin alcohol 4.

Subject	Predicate	Object	Notes	Evidence
leporin ketone 3	is reduced by	LepF short-chain dehydrogenase/reductase	LepF reduces the ketone 3 intermediate formed by LepA, LepG and LepH to the alcohol 4 intermediate that feeds the downstream LepI reaction.	DOI:10.1038/nature23882 https://mite.lisc.univie.ac.at/repository/MITE0000294 https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk https://www.uniprot.org/uniprotkb/B8NJH0 https://www.ncbi.nlm.nih.gov/protein/EED49869.1 reference DOI:10.1038/nature23882 evidence type PRIMARY_EXPERIMENT snippet assayed in the presence of 3 and NADPH, which yielded a single product 4 corresponding to the reduced compound notes Ohashi et al. heterologously coexpressed LepF with LepA, LepG and LepH in Aspergillus nidulans and assayed recombinant LepF from Saccharomyces cerevisiae in vitro with ketone 3 plus NADPH; both experiments support LepF reducing ketone 3 to alcohol 4. reference https://mite.lisc.univie.ac.at/repository/MITE0000294 evidence type DATABASE_ASSERTION retrieved on 2026-10-02 notes MITE0000294 is active and links LepF to UniProtKB:B8NJH0, GenPept EED49869.1, MIBiG BGC0001445, NADP and reduction of a ketone intermediate to a secondary alcohol in the leporin biosynthetic pathway. reference https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-02 notes MIBiG BGC0001445.5 places EED49869.1 in the active Aspergillus flavus NRRL3357 leporin B biosynthetic gene cluster as the AFLA_066910 conserved hypothetical protein locus. reference https://www.uniprot.org/uniprotkb/B8NJH0 evidence type DATABASE_ASSERTION retrieved on 2026-10-02 notes Reviewed UniProtKB:B8NJH0 is the 361 aa Aspergillus flavus NRRL3357 oxidoreductase LepF entry and cross-references EMBL EQ963479 protein EED49869.1. reference https://www.ncbi.nlm.nih.gov/protein/EED49869.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-02 notes NCBI GenPept EED49869.1 is the Aspergillus flavus NRRL3357 conserved hypothetical protein encoded by AFLA_066910 on EQ963479.1.
LepF short-chain dehydrogenase/reductase	forms	leporin alcohol 4	MITE represents the LepF reduction as conversion of the leporin ketone intermediate into the secondary alcohol.	DOI:10.1038/nature23882 https://mite.lisc.univie.ac.at/repository/MITE0000294 https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk https://www.uniprot.org/uniprotkb/B8NJH0 https://www.ncbi.nlm.nih.gov/protein/EED49869.1 reference DOI:10.1038/nature23882 evidence type PRIMARY_EXPERIMENT snippet assayed in the presence of 3 and NADPH, which yielded a single product 4 corresponding to the reduced compound notes Ohashi et al. heterologously coexpressed LepF with LepA, LepG and LepH in Aspergillus nidulans and assayed recombinant LepF from Saccharomyces cerevisiae in vitro with ketone 3 plus NADPH; both experiments support LepF reducing ketone 3 to alcohol 4. reference https://mite.lisc.univie.ac.at/repository/MITE0000294 evidence type DATABASE_ASSERTION retrieved on 2026-10-02 notes MITE0000294 is active and links LepF to UniProtKB:B8NJH0, GenPept EED49869.1, MIBiG BGC0001445, NADP and reduction of a ketone intermediate to a secondary alcohol in the leporin biosynthetic pathway. reference https://mibig.secondarymetabolites.org/repository/BGC0001445.5/BGC0001445.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-02 notes MIBiG BGC0001445.5 places EED49869.1 in the active Aspergillus flavus NRRL3357 leporin B biosynthetic gene cluster as the AFLA_066910 conserved hypothetical protein locus. reference https://www.uniprot.org/uniprotkb/B8NJH0 evidence type DATABASE_ASSERTION retrieved on 2026-10-02 notes Reviewed UniProtKB:B8NJH0 is the 361 aa Aspergillus flavus NRRL3357 oxidoreductase LepF entry and cross-references EMBL EQ963479 protein EED49869.1. reference https://www.ncbi.nlm.nih.gov/protein/EED49869.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-02 notes NCBI GenPept EED49869.1 is the Aspergillus flavus NRRL3357 conserved hypothetical protein encoded by AFLA_066910 on EQ963479.1.

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

Explore across X-Mech

AntibioticMech (leporin B) ↗ MediaIngredientMech (naturalproductmech:mibig-6752ae6cca) ↗ TaxonMech: Aspergillus flavus NRRL3357 (NCBITaxon:332952) ↗ PathwayMech (mibig:BGC0001445) ↗

Provenance

Source concept	Source	Version
BGC0001445	MIBIG	5

This page is generated from data/natural_products/alkaloids/leporin-b.yaml, which is generated from the committed inventories. Neither is edited by hand.