Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000112.1:
Cluster 1Polyketide162616

BGC0000112, neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: neocarzinostatin
PubChem ID: 447545
SMILES string: Copy to clipboard
Molecular formula: C35H33NO12
Average molecular mass: 659.644 Da
Molecular activity: Antibacterial, Cytotoxic
Molecular target: DNA

Class-specific details

Biosynthetic class(es):
Polyketide
Polyketide subclass:
Enediyine (linear)
Polyketide synthase subclass:
Iterative type I / Enediyne type I
Starter unit:
Acetyl-CoA
Polyketide synthase / ketosynthase-encoding genes:
AAM77986,AAM78012
Iterative PKS subtype:
Partially reducing
Number of iterations:
7
Other
Thioesterase type:
Type II
Release / cyclization type:
Unknown

Modular polyketide synthases:
ncsB (AAM77986.1)
Module 1
AT specificity: Malonyl-CoA
Evidence for specificity: Sequence-based prediction
KR stereochemistry: Unknown
Scaffold-modifying domain: None
Module is iterated
Evidence for iteration: Unknown

ncsE (AAM78012.1)
Module 2
AT specificity: Malonyl-CoA
Evidence for specificity: Activity assay
KR stereochemistry: B-group
Scaffold-modifying domain: None
Module is iterated
Evidence for iteration: Unknown

Gene cluster description

neocarzinostatin (BGC0000112). Gene Cluster 1. Biosynthetic class = Polyketide. GenBank AY117439, positions 10097-72712. 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, Enzymatic assays, Gene expression correlated with compound production
MIxS-compliance:Unknown
Contact for this cluster:Xiaohui Yan (The Scripps Research Institute)

Literature references

1. Liu W et al. (2005) The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases. Chem Biol 12(3):293-302. doi: 10.1016/j.chembiol.2004.12.013.
2. Cooke HA et al. (2007) Characterization of NcsB2 as a promiscuous naphthoic acid/coenzyme A ligase integral to the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. J Am Chem Soc 129(25):7728-9. doi: 10.1021/ja071886a. Epub 2007 Jun
3. Zhang J et al. (2008) A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis. Proc Natl Acad Sci U S A 105(5):1460-5. doi: 10.1073/pnas.0711625105.
4. Luo Y et al. (2008) Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. J Biol Chem 283(21):14694-702. doi: 10.1074/jbc.M802206200. Epub
5. Cooke HA et al. (2009) Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. Biochemistry 48(40):9590-8. doi: 10.1021/bi901257q.
6. Lin S et al. (2010) Characterization of the epoxide hydrolase NcsF2 from the neocarzinostatin biosynthetic gene cluster. Org Lett 12(17):3816-9. doi: 10.1021/ol101473t.