Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000247.1:
Cluster 1Polyketide / Saccharide142374

BGC0000247, mithramycin biosynthetic gene cluster from Streptomyces argillaceus. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: mithramycin
SMILES string: Copy to clipboard
Molecular formula: C52H76O24
Exact molecular mass: 1086.15 Da ([M+H]+)
Molecular activity: Cytotoxic
Molecular target: DNA

Class-specific details

Biosynthetic class(es):
Polyketide / Saccharide
Polyketide subclass:
Other (cyclic)
Polyketide synthase subclass:
Type II
Starter unit:
Malonyl-CoA
Polyketide synthase / ketosynthase-encoding genes:
CAA61989.1,CAA61991.1
Genes involved in folding/cyclization:
CAA61987.1 , CAA61988.1 , CAK50782.1

Saccharide subclass:
oligosaccharide
Glycosyltransferases:
CAK50788.1:
Specificity: D-olivose and D-mycarose
Evidence for specificity: Activity assay
CAK50789.1:
Specificity: D-oliose
Evidence for specificity: Knock-out construct
CAK50792.1:
Specificity: D-olivose
Evidence for specificity: Knock-out construct
CAK50793.1:
Specificity: D-olivose
Evidence for specificity: Knock-out construct

Gene cluster description

mithramycin (BGC0000247). Gene Cluster 1. Biosynthetic class = Polyketide/Saccharide. GenBank X89899. Click on genes for more information.

Legend:

biosynthetic genes
transport-related genes
regulatory genes
other genes

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, Sequence-based prediction
MIxS-compliance:Unknown
Contact for this cluster:Jose A. Salas (University of Oviedo)

Literature references

1. Lombo F et al. (1996) Characterization of Streptomyces argillaceus genes encoding a polyketide synthase involved in the biosynthesis of the antitumor mithramycin. Gene 172(1):87-91.
2. Lombo F et al. (1997) Cloning and insertional inactivation of Streptomyces argillaceus genes involved in the earliest steps of biosynthesis of the sugar moieties of the antitumor polyketide mithramycin. J Bacteriol 179(10):3354-7.
3. Prado L et al. (1999) Analysis of two chromosomal regions adjacent to genes for a type II polyketide synthase involved in the biosynthesis of the antitumor polyketide mithramycin in Streptomyces argillaceus. Mol Gen Genet 261(2):216-25.
4. Gonzalez A et al. (2001) The mtmVUC genes of the mithramycin gene cluster in Streptomyces argillaceus are involved in the biosynthesis of the sugar moieties. Mol Gen Genet 264(6):827-35.
5. Blanco G et al. (1996) Deciphering the biosynthetic origin of the aglycone of the aureolic acid group of anti-tumor agents. Chem Biol 3(3):193-6.
6. Lombo F et al. (1996) Characterization of Streptomyces argillaceus genes encoding a polyketide synthase involved in the biosynthesis of the antitumor mithramycin. Gene 172(1):87-91.
7. Fernandez E et al. (1996) An ABC transporter is essential for resistance to the antitumor agent mithramycin in the producer Streptomyces argillaceus. Mol Gen Genet 251(6):692-8.
8. Lombo F et al. (1997) Cloning and insertional inactivation of Streptomyces argillaceus genes involved in the earliest steps of biosynthesis of the sugar moieties of the antitumor polyketide mithramycin. J Bacteriol 179(10):3354-7.
9. Kantola J et al. (1997) Folding of the polyketide chain is not dictated by minimal polyketide synthase in the biosynthesis of mithramycin and anthracycline. Chem Biol 4(10):751-5.
10. Fernandez E et al. (1998) Identification of two genes from Streptomyces argillaceus encoding glycosyltransferases involved in transfer of a disaccharide during biosynthesis of the antitumor drug mithramycin. J Bacteriol 180(18):4929-37.
11. Lombo F et al. (1999) The mithramycin gene cluster of Streptomyces argillaceus contains a positive regulatory gene and two repeated DNA sequences that are located at both ends of the cluster. J Bacteriol 181(2):642-7.
12. Prado L et al. (1999) Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin. Chem Biol 6(1):19-30.
13. Wohlert SE et al. (1999) The structure of mithramycin reinvestigated. J Nat Prod 62(1):119-21. doi: 10.1021/np980355k.
14. Prado L et al. (1999) Analysis of two chromosomal regions adjacent to genes for a type II polyketide synthase involved in the biosynthesis of the antitumor polyketide mithramycin in Streptomyces argillaceus. Mol Gen Genet 261(2):216-25.
15. Blanco G et al. (2000) Characterization of two glycosyltransferases involved in early glycosylation steps during biosynthesis of the antitumor polyketide mithramycin by Streptomyces argillaceus. Mol Gen Genet 262(6):991-1000.
16. Lombo F et al. (2000) The Novel Hybrid Antitumor Compound Premithramycinone H Provides Indirect Evidence for a Tricyclic Intermediate of the Biosynthesis of the Aureolic Acid Antibiotic Mithramycin. Angew Chem Int Ed Engl 39(4):796-799.
17. Lozano MJ et al. (2000) Characterization of two polyketide methyltransferases involved in the biosynthesis of the antitumor drug mithramycin by Streptomyces argillaceus. J Biol Chem 275(5):3065-74.
18. Garcia-Bernardo J et al. (2000) Insertional inactivation of mtrX and mtrY genes from the mithramycin gene cluster affects production and growth of the producer organism Streptomyces argillaceus. FEMS Microbiol Lett 186(1):61-5.
19. Gonzalez A et al. (2001) The mtmVUC genes of the mithramycin gene cluster in Streptomyces argillaceus are involved in the biosynthesis of the sugar moieties. Mol Gen Genet 264(6):827-35.
20. Remsing LL et al. (2002) Ketopremithramycins and ketomithramycins, four new aureolic acid-type compounds obtained upon inactivation of two genes involved in the biosynthesis of the deoxysugar moieties of the antitumor drug mithramycin by Streptomyces argillaceus, reveal novel insights into post-PKS tailoring steps of the mithramycin biosynthetic pathway. J Am Chem Soc 124(8):1606-14.
21. Trefzer A et al. (2002) Rationally designed glycosylated premithramycins: hybrid aromatic polyketides using genes from three different biosynthetic pathways. J Am Chem Soc 124(21):6056-62.
22. Remsing LL et al. (2003) Mithramycin SK, a novel antitumor drug with improved therapeutic index, mithramycin SA, and demycarosyl-mithramycin SK: three new products generated in the mithramycin producer Streptomyces argillaceus through combinatorial biosynthesis. J Am Chem Soc 125(19):5745-53. doi: 10.1021/ja034162h.
23. Rodriguez D et al. (2003) Purification and characterization of a monooxygenase involved in the biosynthetic pathway of the antitumor drug mithramycin. J Bacteriol 185(13):3962-5.
24. Rodriguez D et al. (2004) MtmMII-mediated C-methylation during biosynthesis of the antitumor drug mithramycin is essential for biological activity and DNA-drug interaction. J Biol Chem 279(9):8149-58. doi: 10.1074/jbc.M312351200. Epub 2003
25. Nur-e-Alam M et al. (2005) Elucidation of the glycosylation sequence of mithramycin biosynthesis: isolation of 3A-deolivosylpremithramycin B and its conversion to premithramycin B by glycosyltransferase MtmGII. Chembiochem 6(4):632-6. doi: 10.1002/cbic.200400309.