Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000965.1:
Cluster 1Polyketide185163

BGC0000965, C-1027 biosynthetic gene cluster from Streptomyces globisporus. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: C-1027
PubChem ID: 5281917
SMILES string: Copy to clipboard
Molecular formula: C43H42ClN3O13
Average molecular mass: 844.267 Da
Molecular activity: Antibacterial, Cytotoxic
Molecular target: DNA

Class-specific details

Biosynthetic class(es):
Polyketide
Polyketide subclass:
Enediyine (cyclic)
Polyketide synthase subclass:
Iterative type I / Enediyne type I
Starter unit:
Acetyl-CoA
Polyketide synthase / ketosynthase-encoding genes:
AAL06699
Iterative PKS subtype:
Partially reducing
Number of iterations:
7
Other
Thioesterase type:
Type II
Release / cyclization type:
Unknown

Modular polyketide synthases:
aal06699
Module 1
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

C-1027 (BGC0000965). Gene Cluster 1. Biosynthetic class = Polyketide. GenBank AY048670, positions 5982-78769. 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
MIxS-compliance:Unknown
Contact for this cluster:Xiaohui Yan (The Scripps Research Institute)

Literature references

1. Liu W et al. (2002) Biosynthesis of the enediyne antitumor antibiotic C-1027. Science 297(5584):1170-3. doi: 10.1126/science.1072110.
2. Liu W, Shen B. (2000) Genes for production of the enediyne antitumor antibiotic C-1027 in Streptomyces globisporus are clustered with the cagA gene that encodes the C-1027 apoprotein. Antimicrob Agents Chemother 44(2):382-92.
3. Christenson SD et al. (2003) A novel 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis. J Am Chem Soc 125(20):6062-3. doi: 10.1021/ja034609m.
4. Christenson SD et al. (2003) Kinetic analysis of the 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis. Biochemistry 42(43):12708-18. doi: 10.1021/bi035223r.
5. Murrell JM et al. (2004) Biochemical characterization of the SgcA1 alpha-D-glucopyranosyl-1-phosphate thymidylyltransferase from the enediyne antitumor antibiotic C-1027 biosynthetic pathway and overexpression of sgcA1 in Streptomyces globisporus to improve C-1027 production. J Nat Prod 67(2):206-13. doi: 10.1021/np0340403.
6. Van Lanen SG et al. (2005) Biosynthesis of the beta-amino acid moiety of the enediyne antitumor antibiotic C-1027 featuring beta-amino acyl-S-carrier protein intermediates. J Am Chem Soc 127(33):11594-5. doi: 10.1021/ja052871k.
7. Van Lanen SG et al. (2006) Substrate specificity of the adenylation enzyme SgcC1 involved in the biosynthesis of the enediyne antitumor antibiotic C-1027. J Biol Chem 281(40):29633-40. doi: 10.1074/jbc.M605887200. Epub 2006
8. Kennedy DR et al. (2007) Single chemical modifications of the C-1027 enediyne core, a radiomimetic antitumor drug, affect both drug potency and the role of ataxia-telangiectasia mutated in cellular responses to DNA double-strand breaks. Cancer Res 67(2):773-81. doi: 10.1158/0008-5472.CAN-06-2893.
9. Christianson CV et al. (2007) The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor antibiotic biosynthetic pathway. Biochemistry 46(24):7205-14. doi: 10.1021/bi7003685. Epub 2007 May
10. Lin S et al. (2007) Regiospecific chlorination of (S)-beta-tyrosyl-S-carrier protein catalyzed by SgcC3 in the biosynthesis of the enediyne antitumor antibiotic C-1027. J Am Chem Soc 129(41):12432-8. doi: 10.1021/ja072311g. Epub 2007 Sep
11. Christianson CV et al. (2007) The mechanism of MIO-based aminomutases in beta-amino acid biosynthesis. J Am Chem Soc 129(51):15744-5. doi: 10.1021/ja0762689. Epub 2007 Dec
12. Van Lanen SG et al. (2008) Biosynthesis of the enediyne antitumor antibiotic C-1027 involves a new branching point in chorismate metabolism. Proc Natl Acad Sci U S A 105(2):494-9. doi: 10.1073/pnas.0708750105.
13. Lin S et al. (2008) Characterization of the two-component, FAD-dependent monooxygenase SgcC that requires carrier protein-tethered substrates for the biosynthesis of the enediyne antitumor antibiotic C-1027. J Am Chem Soc 130(20):6616-23. doi: 10.1021/ja710601d. Epub 2008 Apr
14. Lin S et al. (2009) A free-standing condensation enzyme catalyzing ester bond formation in C-1027 biosynthesis. Proc Natl Acad Sci U S A 106(11):4183-8. doi:
15. Van Lanen SG et al. (2009) Characterization of SgcE6, the flavin reductase component supporting FAD-dependent halogenation and hydroxylation in the biosynthesis of the enediyne antitumor antibiotic C-1027. FEMS Microbiol Lett 300(2):237-41. doi:
16. Lin S et al. (2009) Characterization of the SgcF epoxide hydrolase supporting an (R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis. J Am Chem Soc 131(45):16410-7. doi: 10.1021/ja901242s.
17. Chen Y et al. (2010) Manipulation of pathway regulation in Streptomyces globisporus for overproduction of the enediyne antitumor antibiotic C-1027. J Antibiot (Tokyo) 63(8):482-5. doi: 10.1038/ja.2010.55. Epub 2010 Jun
18. Chen Y et al. (2011) Improvement of the enediyne antitumor antibiotic C-1027 production by manipulating its biosynthetic pathway regulation in Streptomyces globisporus. J Nat Prod 74(3):420-4. doi: 10.1021/np100825y. Epub 2011 Jan 21.
19. Lin S et al. (2012) Specificity of the ester bond forming condensation enzyme SgcC5 in C-1027 biosynthesis. Org Lett 14(9):2300-3. doi: 10.1021/ol300720s. Epub 2012 Apr 20.