holomycin

CHEBI:156451 EXACT SEEDED antibacterial

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REVIEWED records curator sign-off on identity, structure, filing class and producer claims; DEPRECATED retains a superseded or out-of-scope record.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 dithiolopyrrolone antibiotic that is 4,5-dihydro[1,2]dithiolo[4,3-b]pyrrole in which the hydrogens at positions 5 and 6 have been replaced by oxo and acetamido groups, respectively. It is an inhibitor of DNA-dependent RNA polymerase, and exhibits antibacterial and antitumour properties.

Structure

Standard InChIKey	HBUNPJGMNVQSBX-UHFFFAOYSA-N
SMILES	CC(=O)NC1=C2C(=CSS2)NC1=O
Stereochemistry	fully defined
Cross-references	npatlas:NPA013565, pubchem:10262683, chembl:CHEMBL476226

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, from MIBiG.

Producer organisms 3

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
Yersinia ruckeri ATCC 29473 NCBITaxon:527005	BGC_CHARACTERIZED	mibig:BGC0002091	PMID:23572522
Photobacterium galatheae NCBITaxon:1654360	BGC_CHARACTERIZED	mibig:BGC0002412	PMID:33771780
Streptomyces clavuligerus ATCC 27064 NCBITaxon:1901	SOURCE_ASSERTION	mibig:BGC0000373	PMID:21041678

Occurrences 25

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
Saccharothrix algeriensis NCBITaxon:173560	CHEBI	PMID:32642829
Streptomyces NCBITaxon:1883	LOTUS	DOI:10.7164/ANTIBIOTICS.30.334
Streptomyces albidoflavus NCBITaxon:1886	LOTUS	DOI:10.1007/S10295-013-1348-5
Streptomyces coelicolor NCBITaxon:1902	LOTUS	DOI:10.1007/S10295-013-1348-5
Streptomyces sp. NCBITaxon:1931	CHEBI	PMID:28627048
Photobacterium halotolerans NCBITaxon:265726	CHEBI	PMID:21339958
Yersinia ruckeri NCBITaxon:29486	LOTUS	DOI:10.1074/JBC.M112.448415
Streptomyces flavovirens NCBITaxon:52258	LOTUS	DOI:10.7717/PEERJ.3601
Streptomyces flavogriseus NCBITaxon:67299	LOTUS	DOI:10.7717/PEERJ.3601
Streptomyces flavogriseus NCBITaxon:67299	CHEBI	PMID:28740758
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1002/CBIC.201200536
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1007/S00253-013-4721-4
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1007/S00253-013-5410-Z
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1016/J.JBIOTEC.2012.09.017
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1021/BI200321C
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1073/PNAS.1014140107
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1111/J.1365-2958.2005.04581.X
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1128/AEM.00916-15
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1128/AEM.01701-18
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1128/AEM.07699-11
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1128/JB.00859-10
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1128/JB.184.23.6559-6565.2002
Streptomyces clavuligerus NCBITaxon:1901	LOTUS	DOI:10.1371/JOURNAL.PONE.0033727
Streptomyces clavuligerus NCBITaxon:1901	CHEBI	PMID:21041678
Streptomyces clavuligerus NCBITaxon:1901	CHEBI	PMID:468729

Biosynthetic gene clusters 3

Accession	Host	Locus evidence	Genome
mibig:BGC0002091	Yersinia ruckeri ATCC 29473 NCBITaxon:527005	CLUSTER_DEMONSTRATED	genbank:ACCC01000028.1
mibig:BGC0002412	Photobacterium galatheae NCBITaxon:1654360	CLUSTER_DEMONSTRATED	genbank:JMIB01000043.1
mibig:BGC0000373	Streptomyces clavuligerus ATCC 27064 NCBITaxon:1901	CLUSTER_UNSTATED	genbank:CM000913.1

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	ORF3488/SCLAV_5271 NRPS UniProtKB:E2PZ83		ungrounded → ungrounded	DOI:10.1073/pnas.1014140107

Step 1: This curates the Streptomyces clavuligerus ATCC 27064 BGC0000373/CM000913 NRPS that activates L-Cys and tethers Cys to its thiolation-domain phosphopantetheinyl arm; later holomycin biosynthetic steps remain uncurated.

Mechanism & Biosynthesis Overview

Causal graph — biosynthesis 4 nodes, 4 edges

Partial Streptomyces clavuligerus holomycin biosynthesis graph for ORF3488/SCLAV_5271 activation and thiolation-domain tethering of L-Cys.

Subject	Predicate	Object	Notes	Evidence
L-Cys	is adenylated by	ORF3488/SCLAV_5271 NRPS	ORF3488 activates L-Cys as L-Cys-AMP in vitro.	DOI:10.1073/pnas.1014140107 https://www.uniprot.org/uniprotkb/E2PZ83 https://www.ncbi.nlm.nih.gov/protein/EFG10344.1 reference DOI:10.1073/pnas.1014140107 evidence type PRIMARY_EXPERIMENT snippet L-Cys-AMP formation and subsequent covalent tethering of Cys notes Li and Walsh purified ORF3488 and demonstrated L-Cys activation and Cys transfer to the phosphopantetheinyl arm of the ORF3488 thiolation domain in vitro. reference https://www.uniprot.org/uniprotkb/E2PZ83 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes Unreviewed UniProtKB:E2PZ83 is the Streptomyces clavuligerus SCLAV_5271 1096 aa non-ribosomal peptide synthetase and cross-references EMBL CM000913 protein EFG10344.1. reference https://www.ncbi.nlm.nih.gov/protein/EFG10344.1 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes NCBI GenPept EFG10344.1 is the SCLAV_5271 non-ribosomal peptide synthetase CDS from the Streptomyces clavuligerus ATCC 27064 CM000913.1 BGC0000373 locus and is sequence-identical to UniProtKB:E2PZ83.
ORF3488/SCLAV_5271 NRPS	forms	L-Cys-AMP	Purified ORF3488 is sufficient for L-Cys-AMP formation.	DOI:10.1073/pnas.1014140107 https://www.uniprot.org/uniprotkb/E2PZ83 https://www.ncbi.nlm.nih.gov/protein/EFG10344.1 reference DOI:10.1073/pnas.1014140107 evidence type PRIMARY_EXPERIMENT snippet L-Cys-AMP formation and subsequent covalent tethering of Cys notes Li and Walsh purified ORF3488 and demonstrated L-Cys activation and Cys transfer to the phosphopantetheinyl arm of the ORF3488 thiolation domain in vitro. reference https://www.uniprot.org/uniprotkb/E2PZ83 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes Unreviewed UniProtKB:E2PZ83 is the Streptomyces clavuligerus SCLAV_5271 1096 aa non-ribosomal peptide synthetase and cross-references EMBL CM000913 protein EFG10344.1. reference https://www.ncbi.nlm.nih.gov/protein/EFG10344.1 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes NCBI GenPept EFG10344.1 is the SCLAV_5271 non-ribosomal peptide synthetase CDS from the Streptomyces clavuligerus ATCC 27064 CM000913.1 BGC0000373 locus and is sequence-identical to UniProtKB:E2PZ83.
L-Cys-AMP	is tethered by	ORF3488/SCLAV_5271 NRPS	ORF3488 tethers Cys to the phosphopantetheinyl arm of its thiolation domain.	DOI:10.1073/pnas.1014140107 https://www.uniprot.org/uniprotkb/E2PZ83 https://www.ncbi.nlm.nih.gov/protein/EFG10344.1 reference DOI:10.1073/pnas.1014140107 evidence type PRIMARY_EXPERIMENT snippet L-Cys-AMP formation and subsequent covalent tethering of Cys notes Li and Walsh purified ORF3488 and demonstrated L-Cys activation and Cys transfer to the phosphopantetheinyl arm of the ORF3488 thiolation domain in vitro. reference https://www.uniprot.org/uniprotkb/E2PZ83 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes Unreviewed UniProtKB:E2PZ83 is the Streptomyces clavuligerus SCLAV_5271 1096 aa non-ribosomal peptide synthetase and cross-references EMBL CM000913 protein EFG10344.1. reference https://www.ncbi.nlm.nih.gov/protein/EFG10344.1 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes NCBI GenPept EFG10344.1 is the SCLAV_5271 non-ribosomal peptide synthetase CDS from the Streptomyces clavuligerus ATCC 27064 CM000913.1 BGC0000373 locus and is sequence-identical to UniProtKB:E2PZ83.
ORF3488/SCLAV_5271 NRPS	forms	NRPS-tethered Cys	The ORF3488 thiolation domain forms an enzyme-tethered Cys intermediate rather than free holomycin.	DOI:10.1073/pnas.1014140107 https://www.uniprot.org/uniprotkb/E2PZ83 https://www.ncbi.nlm.nih.gov/protein/EFG10344.1 reference DOI:10.1073/pnas.1014140107 evidence type PRIMARY_EXPERIMENT snippet L-Cys-AMP formation and subsequent covalent tethering of Cys notes Li and Walsh purified ORF3488 and demonstrated L-Cys activation and Cys transfer to the phosphopantetheinyl arm of the ORF3488 thiolation domain in vitro. reference https://www.uniprot.org/uniprotkb/E2PZ83 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes Unreviewed UniProtKB:E2PZ83 is the Streptomyces clavuligerus SCLAV_5271 1096 aa non-ribosomal peptide synthetase and cross-references EMBL CM000913 protein EFG10344.1. reference https://www.ncbi.nlm.nih.gov/protein/EFG10344.1 evidence type DATABASE_ASSERTION retrieved on 2026-09-27 notes NCBI GenPept EFG10344.1 is the SCLAV_5271 non-ribosomal peptide synthetase CDS from the Streptomyces clavuligerus ATCC 27064 CM000913.1 BGC0000373 locus and is sequence-identical to UniProtKB:E2PZ83.

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

Bioactivities 1

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
USP30 deubiquitinase inhibition: Primary qHTS	ACTIVE	UniProtKB:Q70CQ3	pubchem.aid:1645860 assay USP30 deubiquitinase inhibition: Primary qHTS evidence reference pubchem.aid:1645860 evidence type DATABASE_ASSERTION notes PubChem BioAssay AID 1645860, deposited by 24642; assay type Other. call ACTIVE target enzyme UniProtKB:Q70CQ3

Elsewhere in the fleet

AntibioticMech — CHEBI:156451 (same structure, same inchikey)

Explore across X-Mech

AntibioticMech (holomycin) ↗ MediaIngredientMech (CHEBI:156451) ↗ TaxonMech: Yersinia ruckeri ATCC 29473 (NCBITaxon:527005) ↗ TaxonMech: Photobacterium galatheae (NCBITaxon:1654360) ↗ TaxonMech: Streptomyces clavuligerus ATCC 27064 (NCBITaxon:1901) ↗ PathwayMech (mibig:BGC0002091) ↗ PathwayMech (mibig:BGC0002412) ↗ PathwayMech (mibig:BGC0000373) ↗

Open questions 1

shared-structure — This structure is reported by more than one MIBiG entry: BGC0000373, BGC0002091, BGC0002412. Confirm they describe the same compound rather than an upstream cross-reference error.

Provenance

Source concept	Source	Version
BGC0002091	MIBIG	3
BGC0002412	MIBIG	2
BGC0000373	MIBIG	5
CHEBI:156451	CHEBI	3-star

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