isopenicillin N

CHEBI:18165 EXACT SEEDED antimicrobial unspecified

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REVIEWED records curator sign-off on identity, structure, filing class and producer claims; DEPRECATED retains a superseded or out-of-scope record.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	MIFYHUACUWQUKT-GTQWGBSQSA-N
SMILES	[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)CCC[C@H](N)C(O)=O)C(O)=O
Stereochemistry	fully defined

Filing pathway

Amino acids and peptides — 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, 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 chrysogenum Strain: Wisconsin 54-1255 NCBITaxon:5076	SOURCE_ASSERTION	mibig:BGC0000405	DOI:10.1016/j.fgb.2007.03.008, PMID:1368505 reference DOI:10.1016/j.fgb.2007.03.008 evidence type DATABASE_ASSERTION notes MIBiG BGC0000405 entry version 5; claim-specific citation selected through a reviewed producer_reference correction. This remains a database assertion, not independently graded experimental evidence. reference PMID:1368505 evidence type CURATOR_INFERENCE notes Citation routing only. The imported entry-level reference PMID:1368505 (Smith et al., Bio/Technology 1990;8(1):39-41, DOI:10.1038/nbt0190-39) reports 1990 heterologous cosmid pDJB3-G1 expression in Neurospora crassa and Aspergillus niger and predates GenBank EF601124.1 (coordinates 22186..33473) by 17 years. Route the BGC0000405:2 (isopenicillin N) producer and locus claims to van den Berg et al. 2007 (PMID:17548217, DOI:10.1016/j.fgb.2007.03.008), which sequenced and functionally characterized the 56.8 kb EF601124.1 penicillin cluster in P. chrysogenum Wisconsin 54-1255, without altering taxon, structure identity, or evidence grades. See issue #1023. Original imported citation PMID:1368505 (ENTRY) remains in the raw inventory, not as support for this claim. MIBiG source row BGC0000405:2; SHA256 ae975df0e01f81b73c2e119b776207ca3e0f061375585a06ceef3f099dbbe860. Curator: antigravity; date: 2026-10-23. Taxon, locus, chemistry and evidence grades are unchanged. reference DOI:10.1016/j.fgb.2007.03.008 evidence type CURATOR_INFERENCE notes Strain context: Wisconsin 54-1255. Van den Berg et al. 2007 (PMID:17548217, DOI:10.1016/j.fgb.2007.03.008) and GenBank EF601124.1 explicitly identify Penicillium chrysogenum strain Wisconsin 54-1255 as the sequenced and functionally characterized 56.8 kb penicillin cluster host for BGC0000405:2 (isopenicillin N). Preserve NCBITaxon:5076 and existing SOURCE_ASSERTION/CLUSTER_DEMONSTRATED grades. See issue #1022. Taxon identity and evidence grade are unchanged; this is not a species-wide experiment. MIBiG source row BGC0000405:2; SHA256 ae975df0e01f81b73c2e119b776207ca3e0f061375585a06ceef3f099dbbe860. Curator: antigravity; date: 2026-10-23.

Occurrences 17

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 clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1007/BF01570004
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1111/J.1365-2958.2005.04581.X
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1128/JB.175.3.623-629.1993
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1515/ZNC-2001-9-1020
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.7164/ANTIBIOTICS.35.483
Flavobacterium NCBITaxon:237	LOTUS	DOI:10.1007/BF00428576
Cephalosporium acremonium NCBITaxon:5044	LOTUS	DOI:10.1038/318191A0
Cephalosporium acremonium NCBITaxon:5044	LOTUS	DOI:10.1039/C39830001317
Cephalosporium acremonium NCBITaxon:5044	LOTUS	DOI:10.1039/C39830001319
Cephalosporium acremonium NCBITaxon:5044	LOTUS	DOI:10.1039/C39840001225
Cephalosporium acremonium NCBITaxon:5044	LOTUS	DOI:10.1039/C39860000110
Cephalosporium acremonium NCBITaxon:5044	LOTUS	DOI:10.1039/P19850000369
Sarocladium strictum NCBITaxon:5046	LOTUS	DOI:10.1039/C39830001317
Sarocladium strictum NCBITaxon:5046	LOTUS	DOI:10.1039/C39830001319
Sarocladium strictum NCBITaxon:5046	LOTUS	DOI:10.1039/C39840001225
Sarocladium strictum NCBITaxon:5046	LOTUS	DOI:10.1039/C39860000110
Sarocladium strictum NCBITaxon:5046	LOTUS	DOI:10.1039/P19850000369

Biosynthetic gene clusters 1

Accession	Host	Locus evidence	Genome
mibig:BGC0000405	Penicillium chrysogenum NCBITaxon:5076	CLUSTER_DEMONSTRATED	genbank:EF601124.1

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	PcbAB ACV synthetase UniProtKB:A6N339	RHEA:23196	CHEBI:58672 + CHEBI:35235 + CHEBI:57762 + CHEBI:30616 + CHEBI:15377 → CHEBI:58572 + CHEBI:456215 + CHEBI:33019 + CHEBI:15378	DOI:10.1042/bj3270185
2	Isopenicillin N synthase UniProtKB:B6HLU0	RHEA:22428	CHEBI:58572 → CHEBI:18165	DOI:10.1016/j.fgb.2007.03.008

Step 1: Penicillium chrysogenum PcbAB condenses L-2-aminoadipate, L-cysteine, and L-valine to the ACV tripeptide. RHEA:23196 also consumes three ATP and water and releases three AMP, three diphosphates, and three H(+).

Step 2: Penicillium rubens/Penicillium chrysogenum Wisconsin 54-1255 IpnA/PcbC oxidatively cyclizes ACV to isopenicillin N. RHEA:22428 also consumes O2 and releases water; its product participant is CHEBI:58399 isopenicillin N(1-), while this record is grounded to neutral CHEBI:18165 with the same stereochemistry.

Mechanism & Biosynthesis Overview

Causal graph — biosynthesis 7 nodes, 6 edges

Penicillium rubens / Penicillium chrysogenum Wisconsin 54-1255 BGC0000405 two-step biosynthesis of isopenicillin N: PcbAB-catalyzed ATP-dependent condensation of L-2-aminoadipate, L-cysteine, and L-valine to ACV followed by IpnA-catalyzed oxidative cyclization of ACV to isopenicillin N.

Subject	Predicate	Object	Notes	Evidence
L-2-aminoadipate	is condensed by	PcbAB	RHEA:23196 places L-2-aminoadipate on the substrate side of the PcbAB ATP-dependent ACV synthase reaction.	DOI:10.1042/bj3270185 DOI:10.1038/nbt0190-39 DOI:10.1016/j.fgb.2007.03.008 https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ https://www.uniprot.org/uniprotkb/A6N339 https://www.rhea-db.org/rhea/23196 reference DOI:10.1042/bj3270185 evidence type PRIMARY_EXPERIMENT snippet ACVS from Penicillium chrysogenum was purified to homogeneity notes Thelen et al. purified Penicillium chrysogenum ACV synthetase and characterized ATP/PPi exchange and tripeptide-forming activity for the ACV building-block amino acids. reference DOI:10.1038/nbt0190-39 evidence type PRIMARY_EXPERIMENT snippet possessed delta-(L-alpha-amino-adipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthetase notes Smith et al. heterologously expressed a Penicillium chrysogenum cosmid carrying the penicillin biosynthetic cluster and detected ACVS and IPNS enzyme activity in transformed fungal hosts. reference DOI:10.1016/j.fgb.2007.03.008 evidence type PRIMARY_EXPERIMENT snippet genes encoding the three penicillin biosynthetic enzymes alone are sufficient to restore full beta-lactam synthesis notes Van den Berg et al. functionally characterized the Penicillium chrysogenum Wisconsin 54-1255 EF601124 penicillin cluster that carries pcbAB, pcbC, and penDE. reference https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG entry version 5 links BGC0000405 to the Penicillium chrysogenum EF601124.1 NRPS cluster for ACV, isopenicillin N, and benzylpenicillin; the EF601124.1 record contains pcbAB / ABR12615.1 annotated as ACV synthetase. reference https://www.uniprot.org/uniprotkb/A6N339 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes UniProtKB:A6N339 is the Penicillium chrysogenum pcbAB/ABR12615.1 ACV synthetase from EMBL EF601124 and annotates the RHEA:23196 / left-to-right RHEA:23197 ACV synthase reaction. reference https://www.rhea-db.org/rhea/23196 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes RHEA:23196 is the ATP-dependent condensation of L-2-aminoadipate, L-cysteine, and L-valine to ACV, AMP, diphosphate, and H(+).
L-cysteine	is condensed by	PcbAB	RHEA:23196 places L-cysteine on the substrate side of the PcbAB ATP-dependent ACV synthase reaction.	DOI:10.1042/bj3270185 DOI:10.1038/nbt0190-39 DOI:10.1016/j.fgb.2007.03.008 https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ https://www.uniprot.org/uniprotkb/A6N339 https://www.rhea-db.org/rhea/23196 reference DOI:10.1042/bj3270185 evidence type PRIMARY_EXPERIMENT snippet ACVS from Penicillium chrysogenum was purified to homogeneity notes Thelen et al. purified Penicillium chrysogenum ACV synthetase and characterized ATP/PPi exchange and tripeptide-forming activity for the ACV building-block amino acids. reference DOI:10.1038/nbt0190-39 evidence type PRIMARY_EXPERIMENT snippet possessed delta-(L-alpha-amino-adipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthetase notes Smith et al. heterologously expressed a Penicillium chrysogenum cosmid carrying the penicillin biosynthetic cluster and detected ACVS and IPNS enzyme activity in transformed fungal hosts. reference DOI:10.1016/j.fgb.2007.03.008 evidence type PRIMARY_EXPERIMENT snippet genes encoding the three penicillin biosynthetic enzymes alone are sufficient to restore full beta-lactam synthesis notes Van den Berg et al. functionally characterized the Penicillium chrysogenum Wisconsin 54-1255 EF601124 penicillin cluster that carries pcbAB, pcbC, and penDE. reference https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG entry version 5 links BGC0000405 to the Penicillium chrysogenum EF601124.1 NRPS cluster for ACV, isopenicillin N, and benzylpenicillin; the EF601124.1 record contains pcbAB / ABR12615.1 annotated as ACV synthetase. reference https://www.uniprot.org/uniprotkb/A6N339 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes UniProtKB:A6N339 is the Penicillium chrysogenum pcbAB/ABR12615.1 ACV synthetase from EMBL EF601124 and annotates the RHEA:23196 / left-to-right RHEA:23197 ACV synthase reaction. reference https://www.rhea-db.org/rhea/23196 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes RHEA:23196 is the ATP-dependent condensation of L-2-aminoadipate, L-cysteine, and L-valine to ACV, AMP, diphosphate, and H(+).
L-valine	is condensed by	PcbAB	RHEA:23196 places L-valine on the substrate side of the PcbAB ATP-dependent ACV synthase reaction.	DOI:10.1042/bj3270185 DOI:10.1038/nbt0190-39 DOI:10.1016/j.fgb.2007.03.008 https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ https://www.uniprot.org/uniprotkb/A6N339 https://www.rhea-db.org/rhea/23196 reference DOI:10.1042/bj3270185 evidence type PRIMARY_EXPERIMENT snippet ACVS from Penicillium chrysogenum was purified to homogeneity notes Thelen et al. purified Penicillium chrysogenum ACV synthetase and characterized ATP/PPi exchange and tripeptide-forming activity for the ACV building-block amino acids. reference DOI:10.1038/nbt0190-39 evidence type PRIMARY_EXPERIMENT snippet possessed delta-(L-alpha-amino-adipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthetase notes Smith et al. heterologously expressed a Penicillium chrysogenum cosmid carrying the penicillin biosynthetic cluster and detected ACVS and IPNS enzyme activity in transformed fungal hosts. reference DOI:10.1016/j.fgb.2007.03.008 evidence type PRIMARY_EXPERIMENT snippet genes encoding the three penicillin biosynthetic enzymes alone are sufficient to restore full beta-lactam synthesis notes Van den Berg et al. functionally characterized the Penicillium chrysogenum Wisconsin 54-1255 EF601124 penicillin cluster that carries pcbAB, pcbC, and penDE. reference https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG entry version 5 links BGC0000405 to the Penicillium chrysogenum EF601124.1 NRPS cluster for ACV, isopenicillin N, and benzylpenicillin; the EF601124.1 record contains pcbAB / ABR12615.1 annotated as ACV synthetase. reference https://www.uniprot.org/uniprotkb/A6N339 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes UniProtKB:A6N339 is the Penicillium chrysogenum pcbAB/ABR12615.1 ACV synthetase from EMBL EF601124 and annotates the RHEA:23196 / left-to-right RHEA:23197 ACV synthase reaction. reference https://www.rhea-db.org/rhea/23196 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes RHEA:23196 is the ATP-dependent condensation of L-2-aminoadipate, L-cysteine, and L-valine to ACV, AMP, diphosphate, and H(+).
PcbAB	forms	N-[(5S)-5-ammonio-5-carboxylatopentanoyl]-L-cysteinyl-D-valinate	RHEA:23196 places ACV on the product side of the PcbAB ATP-dependent ACV synthase reaction.	DOI:10.1042/bj3270185 DOI:10.1038/nbt0190-39 DOI:10.1016/j.fgb.2007.03.008 https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ https://www.uniprot.org/uniprotkb/A6N339 https://www.rhea-db.org/rhea/23196 reference DOI:10.1042/bj3270185 evidence type PRIMARY_EXPERIMENT snippet ACVS from Penicillium chrysogenum was purified to homogeneity notes Thelen et al. purified Penicillium chrysogenum ACV synthetase and characterized ATP/PPi exchange and tripeptide-forming activity for the ACV building-block amino acids. reference DOI:10.1038/nbt0190-39 evidence type PRIMARY_EXPERIMENT snippet possessed delta-(L-alpha-amino-adipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthetase notes Smith et al. heterologously expressed a Penicillium chrysogenum cosmid carrying the penicillin biosynthetic cluster and detected ACVS and IPNS enzyme activity in transformed fungal hosts. reference DOI:10.1016/j.fgb.2007.03.008 evidence type PRIMARY_EXPERIMENT snippet genes encoding the three penicillin biosynthetic enzymes alone are sufficient to restore full beta-lactam synthesis notes Van den Berg et al. functionally characterized the Penicillium chrysogenum Wisconsin 54-1255 EF601124 penicillin cluster that carries pcbAB, pcbC, and penDE. reference https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG entry version 5 links BGC0000405 to the Penicillium chrysogenum EF601124.1 NRPS cluster for ACV, isopenicillin N, and benzylpenicillin; the EF601124.1 record contains pcbAB / ABR12615.1 annotated as ACV synthetase. reference https://www.uniprot.org/uniprotkb/A6N339 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes UniProtKB:A6N339 is the Penicillium chrysogenum pcbAB/ABR12615.1 ACV synthetase from EMBL EF601124 and annotates the RHEA:23196 / left-to-right RHEA:23197 ACV synthase reaction. reference https://www.rhea-db.org/rhea/23196 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes RHEA:23196 is the ATP-dependent condensation of L-2-aminoadipate, L-cysteine, and L-valine to ACV, AMP, diphosphate, and H(+).
N-[(5S)-5-ammonio-5-carboxylatopentanoyl]-L-cysteinyl-D-valinate	is oxidatively cyclized by	IpnA	RHEA:22428 represents the O2-dependent EC:1.21.3.1 reaction that consumes ACV and releases water.	DOI:10.1016/j.fgb.2007.03.008 DOI:10.1038/nbt0190-39 https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ RHEA:22428 https://www.uniprot.org/uniprotkb/B6HLU0 reference DOI:10.1016/j.fgb.2007.03.008 evidence type PRIMARY_EXPERIMENT snippet genes encoding the three penicillin biosynthetic enzymes alone are sufficient to restore full beta-lactam synthesis notes Van den Berg et al. functionally characterized the Penicillium chrysogenum Wisconsin54-1255 EF601124 penicillin cluster and showed that pcbAB, pcbC, and penDE were sufficient for full beta-lactam synthesis in a mutant lacking the complete region. reference DOI:10.1038/nbt0190-39 evidence type PRIMARY_EXPERIMENT snippet possessed delta-(L-alpha-amino-adipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthetase (IPNS) notes Smith et al. heterologously expressed a Penicillium chrysogenum cosmid carrying the penicillin biosynthetic gene cluster and detected IPNS enzyme activity in transformed fungal hosts. reference https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ evidence type DATABASE_ASSERTION retrieved on 2026-09-30 notes MIBiG entry version 5 links BGC0000405 to the Penicillium chrysogenum EF601124.1 NRPS cluster for ACV, isopenicillin N, and benzylpenicillin. reference RHEA:22428 evidence type DATABASE_ASSERTION retrieved on 2026-09-30 notes RHEA:22428 annotates EC:1.21.3.1 as N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine plus O2 forming isopenicillin N and water. reference https://www.uniprot.org/uniprotkb/B6HLU0 evidence type DATABASE_ASSERTION retrieved on 2026-09-30 notes Reviewed UniProtKB:B6HLU0 is Penicillium rubens strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255 IpnA, an isopenicillin N synthase annotated with RHEA:22428.
IpnA	forms	isopenicillin N	RHEA uses the isopenicillin N conjugate base CHEBI:58399 as the product participant; this graph points at neutral CHEBI:18165, the exact structure recorded for BGC0000405 compound 2.	DOI:10.1016/j.fgb.2007.03.008 DOI:10.1038/nbt0190-39 https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ RHEA:22428 https://www.uniprot.org/uniprotkb/B6HLU0 reference DOI:10.1016/j.fgb.2007.03.008 evidence type PRIMARY_EXPERIMENT snippet genes encoding the three penicillin biosynthetic enzymes alone are sufficient to restore full beta-lactam synthesis notes Van den Berg et al. functionally characterized the Penicillium chrysogenum Wisconsin54-1255 EF601124 penicillin cluster and showed that pcbAB, pcbC, and penDE were sufficient for full beta-lactam synthesis in a mutant lacking the complete region. reference DOI:10.1038/nbt0190-39 evidence type PRIMARY_EXPERIMENT snippet possessed delta-(L-alpha-amino-adipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthetase (IPNS) notes Smith et al. heterologously expressed a Penicillium chrysogenum cosmid carrying the penicillin biosynthetic gene cluster and detected IPNS enzyme activity in transformed fungal hosts. reference https://mibig.secondarymetabolites.org/repository/BGC0000405.5/ evidence type DATABASE_ASSERTION retrieved on 2026-09-30 notes MIBiG entry version 5 links BGC0000405 to the Penicillium chrysogenum EF601124.1 NRPS cluster for ACV, isopenicillin N, and benzylpenicillin. reference RHEA:22428 evidence type DATABASE_ASSERTION retrieved on 2026-09-30 notes RHEA:22428 annotates EC:1.21.3.1 as N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine plus O2 forming isopenicillin N and water. reference https://www.uniprot.org/uniprotkb/B6HLU0 evidence type DATABASE_ASSERTION retrieved on 2026-09-30 notes Reviewed UniProtKB:B6HLU0 is Penicillium rubens strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255 IpnA, an isopenicillin N synthase annotated with RHEA:22428.

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

Elsewhere in the fleet

AntibioticMech — CHEBI:18165 (same structure, same inchikey)

Explore across X-Mech

AntibioticMech (isopenicillin N) ↗ MediaIngredientMech (CHEBI:18165) ↗ TaxonMech: Penicillium chrysogenum (NCBITaxon:5076) ↗ PathwayMech (mibig:BGC0000405) ↗

Provenance

Source concept	Source	Version
BGC0000405	MIBIG	5
CHEBI:18165	CHEBI	3-star

This page is generated from data/natural_products/amino_acids_and_peptides/isopenicillin-n.yaml, which is generated from the committed inventories. Neither is edited by hand.