K-252a

CHEBI:43616 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REVIEWED records curator sign-off on identity, structure, filing class and producer claims; DEPRECATED retains a superseded or out-of-scope record.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.

A organic heterooctacyclic compound that is a potent inhibitor of protein kinase C and is isolated from Nocardiopsis sp K-252a

Structure

Standard InChIKey	KOZFSFOOLUUIGY-SOLYNIJKSA-N
SMILES	C[C@@]12[C@](C[C@@H](O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)(C(=O)OC)O
Stereochemistry	fully defined
Cross-references	pubchem:3035817

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 other, 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
Nonomuraea longicatena NCBITaxon:83682	SOURCE_ASSERTION	mibig:BGC0000814	DOI:10.7164/antibiotics.39.1059

Occurrences 5

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
Actinomadura NCBITaxon:1988	LOTUS	DOI:10.7164/ANTIBIOTICS.38.1437
Nocardiopsis NCBITaxon:2013	LOTUS	DOI:10.7164/ANTIBIOTICS.39.1059
Streptomyces longisporoflavus NCBITaxon:28044	LOTUS	DOI:10.7164/ANTIBIOTICS.49.1060
Streptomyces longisporoflavus NCBITaxon:28044	LOTUS	DOI:10.7164/ANTIBIOTICS.49.519
Nocardiopsis sp. K-252a NCBITaxon:310350	CHEBI	PMID:3759657

Biosynthetic gene clusters 1

Accession	Host	Locus evidence	Genome
mibig:BGC0000814	Nonomuraea longicatena NCBITaxon:83682	CLUSTER_UNSTATED	genbank:FJ031030.1

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.

Mechanism & Biosynthesis Overview

Causal graph — bioactivity 2 nodes, 1 edge

K-252a binds an engineered human MET receptor tyrosine kinase domain.

Subject	Predicate	Object	Notes	Evidence
K-252a	binds	human hepatocyte growth factor receptor	PubChem BioAssay AID 977611 maps this exact Standard InChIKey to a 0.01 uM Kd row for PDB 1R0P chain A; PDB 1R0P maps chain A to UniProtKB:P08581 residues 1049-1360 and records the KSA K-252A ligand bound to an engineered kinase-domain construct carrying Y1194F, Y1234F, Y1235D, and V1272L substitutions.	DOI:10.1073/pnas.1734128100 DOI:10.2210/pdb1r0p/pdb reference DOI:10.1073/pnas.1734128100 evidence type PRIMARY_EXPERIMENT snippet Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a notes PDB 1R0P is the K-252a-bound structure described by Schiering et al.; PubChem reports its PDB-derived 10 nM Kd for this exact Standard InChIKey. reference DOI:10.2210/pdb1r0p/pdb evidence type DATABASE_ASSERTION notes RCSB PDB identifies 1R0P as a human c-Met tyrosine kinase domain structure in complex with KSA K-252A and maps entity 1 chain A to UniProtKB:P08581.

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

Causal graph — biosynthesis 8 nodes, 7 edges

Partial K-252a biosynthesis evidence anchored to the record's FJ031030.1 nok cluster: crude-extract precursor production and a separate InkE/NokD FAD-binding assay. These experiments do not establish complete K-252a synthesis, sugar stereochemistry, or individual NokC/NokD turnover.

Subject	Predicate	Object	Notes	Evidence
NokA	contributes to	NokABCD-expressing E. coli crude-extract reaction	pCY20 expresses untagged NokABCD with native stops; pG-KJE7 supplies folding chaperones in E. coli BL21(DE3). Not a purified two-enzyme assay or demonstrated stable complex (Methods; Figs. 6-8).	DOI:10.1039/b905293c https://www.uniprot.org/uniprotkb/Q27IF4 reference DOI:10.1039/b905293c evidence type PRIMARY_EXPERIMENT reference https://www.uniprot.org/uniprotkb/Q27IF4 evidence type DATABASE_ASSERTION notes Canonical 486-aa sequence exactly matches FJ031030.1 CDS ACN29719.1 (nokA), Nonomuraea longicatena taxon 83682, strain NRRL 15532/K-252. Current UniProt locus annotations differ from the original gene names; grounding uses the entire translated sequence, not label similarity. retrieved on 2026-10-03
NokB	contributes to	NokABCD-expressing E. coli crude-extract reaction		DOI:10.1039/b905293c https://www.uniprot.org/uniprotkb/Q27IF3 reference DOI:10.1039/b905293c evidence type PRIMARY_EXPERIMENT reference https://www.uniprot.org/uniprotkb/Q27IF3 evidence type DATABASE_ASSERTION notes Canonical 1031-aa sequence exactly matches FJ031030.1 CDS ACN29720.1 (nokB), Nonomuraea longicatena taxon 83682, strain NRRL 15532/K-252. Current UniProt locus annotations differ from the original gene names; grounding uses the entire translated sequence, not label similarity. retrieved on 2026-10-03
NokC	was coexpressed for	NokABCD-expressing E. coli crude-extract reaction	Assay participant only: soluble expression does not demonstrate NokC catalysis; the measured product was CPA, not K-252c.	DOI:10.1039/b905293c https://www.uniprot.org/uniprotkb/C9W353 reference DOI:10.1039/b905293c evidence type PRIMARY_EXPERIMENT reference https://www.uniprot.org/uniprotkb/C9W353 evidence type DATABASE_ASSERTION notes Canonical 409-aa sequence exactly matches FJ031030.1 CDS ACN29722.1 (nokC), Nonomuraea longicatena taxon 83682, strain NRRL 15532/K-252. Current UniProt locus annotations differ from the original gene names; grounding uses the entire translated sequence, not label similarity. retrieved on 2026-10-03
NokD / InkE	was coexpressed for	NokABCD-expressing E. coli crude-extract reaction	Assay participant only; no individual NokD turnover is established.	DOI:10.1039/b905293c https://www.uniprot.org/uniprotkb/Q27IF2 reference DOI:10.1039/b905293c evidence type PRIMARY_EXPERIMENT reference https://www.uniprot.org/uniprotkb/Q27IF2 evidence type DATABASE_ASSERTION notes Canonical 525-aa sequence exactly matches FJ031030.1 CDS ACN29721.1 (nokD), Nonomuraea longicatena taxon 83682, strain NRRL 15532/K-252. Current UniProt locus annotations differ from the original gene names; grounding uses the entire translated sequence, not label similarity. retrieved on 2026-10-03
L-tryptophan	is supplied to	NokABCD-expressing E. coli crude-extract reaction	Methods: 2 mM L-tryptophan, 40 uL extract in 52 uL, 80 mM Tris-HCl pH 7.8, 7.6% glycerol; 30 C for 24 h.	DOI:10.1039/b905293c reference DOI:10.1039/b905293c evidence type PRIMARY_EXPERIMENT
NokABCD-expressing E. coli crude-extract reaction	produces	Chromopyrrolic acid		DOI:10.1039/b905293c reference DOI:10.1039/b905293c evidence type PRIMARY_EXPERIMENT snippet the cell-free crude extract of the NokABCD proteins notes Figs. 8-9 and product-characterization methods: HPLC time-zero comparison and isolated-product NMR support CPA formation. The printed exact-mass values disagree with the calculated masses; they are not used as confirming exact-mass evidence.
NokD / InkE	binds	FAD	Table 2: InkE ITC Kd = 59 +/- 48 uM, four experiments. Separate Ni-affinity-purified InkE preparation from Rosetta 2(DE3) pLysS, not the untagged pCY20 extract. As-isolated apo protein was titrated with FAD in 150 mM NaCl, 25 mM HEPES pH 7.5, 10% glycerol. Binding alone does not demonstrate monooxygenation or product turnover.	DOI:10.1016/j.chembiol.2012.05.016 https://ars.els-cdn.com/content/image/1-s2.0-S1074552112001809-mmc1.pdf https://rest.uniprot.org/uniparc/UPI00006CA182 reference DOI:10.1016/j.chembiol.2012.05.016 evidence type PRIMARY_EXPERIMENT snippet purifies without bound FAD notes Table 2: reported uncertainty retained without assigning an unstated SD/SEM statistic. reference https://ars.els-cdn.com/content/image/1-s2.0-S1074552112001809-mmc1.pdf evidence type PRIMARY_EXPERIMENT notes Fig. S2C and caption: ITC at 25 C. SI pp. 18-19: pET28a InkE recombinant construct; canonical identifier excludes its affinity tag. reference https://rest.uniprot.org/uniparc/UPI00006CA182 evidence type DATABASE_ASSERTION notes Active cross-references link Q27IF2, InkE ABD59214.1 (DQ399653.1), and NokD ACN29721.1 (FJ031030.1). All three 525-aa sequences and SI Fig. S1 InkE agree exactly; the published InkE primer target regions also match. retrieved on 2026-10-03

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

Elsewhere in the fleet

AntibioticMech — CHEBI:43616 (same structure, same inchikey)

Explore across X-Mech

AntibioticMech (K-252a) ↗ MediaIngredientMech (CHEBI:43616) ↗ TaxonMech: Nonomuraea longicatena (NCBITaxon:83682) ↗ PathwayMech (mibig:BGC0000814) ↗

Provenance

Source concept	Source	Version
BGC0000814	MIBIG	3
CHEBI:43616	CHEBI	3-star

This page is generated from data/natural_products/alkaloids/k-252a.yaml, which is generated from the committed inventories. Neither is edited by hand.