Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000963.1:
Cluster 1NRP / Polyketide / Saccharide177457

BGC0000963, bleomycin biosynthetic gene cluster from Streptomyces verticillus. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: bleomycin
PubChem ID: 84068
SMILES string: Copy to clipboard
Molecular formula: C55H84N17O21S3+
Average molecular mass: 1415.555 Da
Molecular activity: Cytotoxic
Molecular target: DNA

Class-specific details

Biosynthetic class(es):
NRP / Polyketide / Saccharide
Glycopeptide (linear)
Thioesterase type:
None
Release / cyclization type:
Unknown

Nonribosomal peptide synthetases:
blmX (AAG02355.1)
Module 8
A specificity: Histidine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Module 9
A specificity: Asparigine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
blmIX (AAG02356.1)
Module 7
A specificity: Alanine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
blmVII (AAG02358.1)
Module 6
A specificity: Threonine
Evidence for specificity: Structure-based inference
C domain subtype: LCL
blmVI (AAG02359.1)
Module 3
A specificity: Asparigine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Module 4
A specificity: Serine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Module 5
A specificity: Unknown
Evidence for specificity: Unknown
C domain subtype: Starter
blmV (AAG02360.1)
Module 3
A specificity: Asparigine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
blmIV (AAG02364.1)
Module 0
A specificity: Cysteine
Evidence for specificity: Sequence-based prediction
C domain subtype: Heterocyclization
Scaffold-modifying domain: Oxidation
Module 1
A specificity: Cysteine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Scaffold-modifying domain: Other
Module 2
A specificity: Beta-alanine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Polyketide subclass:
Other (linear)
Polyketide synthase subclass:
Modular type I
Starter unit:
Other
Thioesterase type:
None
Release / cyclization type:
Other

Modular polyketide synthases:
blmVIII (AAG02357.1)
Module 7
AT specificity: Malonyl-CoA
Evidence for specificity: Structure-based inference
KR stereochemistry: A-group
Scaffold-modifying domain: Methylation

Gene cluster description

bleomycin (BGC0000963). Gene Cluster 1. Biosynthetic class = NRP/Polyketide/Saccharide. GenBank AF210249, positions 18823-77457. Click on genes for more information.

Legend:

biosynthetic genes
transport-related genes
regulatory genes
other genes

Domain annotation

Homologous known gene clusters

General MIBiG information on this cluster

Complete gene cluster sequence?complete
Evidence for cluster-compound connection:Knock-out studies, Heterologous expression
MIxS-compliance:Unknown
Contact for this cluster:Xiaohui Yan (The Scripps Research Institute)

Literature references

1. Du L, Shen B. (1999) Identification and characterization of a type II peptidyl carrier protein from the bleomycin producer Streptomyces verticillus ATCC 15003. Chem Biol 6(8):507-17. doi: 10.1016/S1074-5521(99)80083-0.
2. Du L et al. (2000) The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase. Chem Biol 7(8):623-42.
3. Du L et al. (2000) An oxidation domain in the BlmIII non-ribosomal peptide synthetase probably catalyzing thiazole formation in the biosynthesis of the anti-tumor drug bleomycin in Streptomyces verticillus ATCC15003. FEMS Microbiol Lett 189(2):171-5.
4. Sanchez C et al. (2001) Cloning and characterization of a phosphopantetheinyl transferase from Streptomyces verticillus ATCC15003, the producer of the hybrid peptide-polyketide antitumor drug bleomycin. Chem Biol 8(7):725-38.
5. Du L et al. (2003) BlmIII and BlmIV nonribosomal peptide synthetase-catalyzed biosynthesis of the bleomycin bithiazole moiety involving both in cis and in trans aminoacylation. Biochemistry 42(32):9731-40. doi: 10.1021/bi034817r.
6. Schneider TL et al. (2003) Oxidase domains in epothilone and bleomycin biosynthesis: thiazoline to thiazole oxidation during chain elongation. Biochemistry 42(32):9722-30. doi: 10.1021/bi034792w.
7. Galm U et al. (2008) In vivo manipulation of the bleomycin biosynthetic gene cluster in Streptomyces verticillus ATCC15003 revealing new insights into its biosynthetic pathway. J Biol Chem 283(42):28236-45. doi: 10.1074/jbc.M804971200. Epub 2008
8. Galm U et al. (2011) Comparative analysis of the biosynthetic gene clusters and pathways for three structurally related antitumor antibiotics: bleomycin, tallysomycin, and zorbamycin. J Nat Prod 74(3):526-36. doi: 10.1021/np1008152. Epub 2011 Jan 6.
9. Huang SX et al. (2012) A designer bleomycin with significantly improved DNA cleavage activity. J Am Chem Soc 134(32):13501-9. doi: 10.1021/ja3056535. Epub 2012 Aug