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Cluster information : Mithramycin


close this sectionCompound

Entry nameMithramycin
SynonymPlicamycin
PKS TypeTypeII
Starter Unitacetyl-CoA
Chain Length10
Sugar UnitD-olivose
D-mycarose
D-oliose
ClassificationAureolic acid
ActivityAntibacterial
Antitumor
CompositionC52H76O24
Mithramycin

close this sectionOriginal source

Organism
StrainATCC 12956
Contig
Click on the icon to see Genetic map.

close this sectionPKS/NRPS Module

KS3..374
CLF7..364
ACP2..75

close this sectionReference

Characterization of Streptomyces argillaceus genes encoding a polyketide synthase involved in the biosynthesis of the antitumor mithramycin.
Lombo F, Blanco G, Fernandez E, Mendez C, Salas JA
[PMID: 8654997]Gene. 172 (1996) 87-91
An ABC transporter is essential for resistance to the antitumor agent mithramycin in the producer Streptomyces argillaceus.
Fernandez E, Lombo F, Mendez C, Salas JA
[PMID: 8757400]Mol Gen Genet. 251 (1996) 692-8
Cloning and insertional inactivation of Streptomyces argillaceus genes involved in the earliest steps of biosynthesis of the sugar moieties of the antitumor polyketide mithramycin.
Lombo F, Siems K, Brana AF, Mendez C, Bindseil K, Salas JA
[PMID: 9150235]J Bacteriol. 179 (1997) 3354-7
Identification of two genes from Streptomyces argillaceus encoding glycosyltransferases involved in transfer of a disaccharide during biosynthesis of the antitumor drug mithramycin.
Fernandez E, Weissbach U, Sanchez Reillo C, Brana AF, Mendez C, Rohr J, Salas JA
[PMID: 9733697]J Bacteriol. 180 (1998) 4929-37
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.
Lombo F, Brana AF, Mendez C, Salas JA
[PMID: 9882681]J Bacteriol. 181 (1999) 642-7
Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin.
Prado L, Fernandez E, Weissbach U, Blanco G, Quiros LM, Brana AF, Mendez C, Rohr J, Salas JA
[PMID: 9889148]Chem Biol. 6 (1999) 19-30
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.
Prado L, Lombo F, Brana AF, Mendez C, Rohr J, Salas JA
[PMID: 10102355]Mol Gen Genet. 261 (1999) 216-25
Characterization of two polyketide methyltransferases involved in the biosynthesis of the antitumor drug mithramycin by Streptomyces argillaceus.
Lozano MJ, Remsing LL, Quiros LM, Brana AF, Fernandez E, Sanchez C, Mendez C, Rohr J, Salas JA
[PMID: 10652287]J Biol Chem. 275 (2000) 3065-74
Characterization of two glycosyltransferases involved in early glycosylation steps during biosynthesis of the antitumor polyketide mithramycin by Streptomyces argillaceus.
Blanco G, Fernandez E, Fernandez MJ, Brana AF, Weissbach U, Kunzel E, Rohr J, Mendez C, Salas JA
[PMID: 10660060]Mol Gen Genet. 262 (2000) 991-1000
Insertional inactivation of mtrX and mtrY genes from the mithramycin gene cluster affects production and growth of the producer organism Streptomyces argillaceus.
Garcia-Bernardo J, Brana AF, Mendez C, Salas JA
[PMID: 10779713]FEMS Microbiol Lett. 186 (2000) 61-5
The mtmVUC genes of the mithramycin gene cluster in Streptomyces argillaceus are involved in the biosynthesis of the sugar moieties.
Gonzalez A, Remsing LL, Lombo F, Fernandez MJ, Prado L, Brana AF, Kunzel E, Rohr J, Mendez C, Salas JA
[PMID: 11254130]Mol Gen Genet. 264 (2001) 827-35
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.
Remsing LL, Garcia-Bernardo J, Gonzalez A, Kunzel E, Rix U, Brana AF, Bearden DW, Mendez C, Salas JA, Rohr J
[PMID: 11853433]J Am Chem Soc. 124 (2002) 1606-14
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.
Remsing LL, Gonzalez AM, Nur-e-Alam M, Fernandez-Lozano MJ, Brana AF, Rix U, Oliveira MA, Mendez C, Salas JA, Rohr J
[PMID: 12733914]J Am Chem Soc. 125 (2003) 5745-53
Purification and characterization of a monooxygenase involved in the biosynthetic pathway of the antitumor drug mithramycin.
Rodriguez D, Quiros LM, Brana AF, Salas JA
[PMID: 12813091]J Bacteriol. 185 (2003) 3962-5
MtmMII-mediated C-methylation during biosynthesis of the antitumor drug mithramycin is essential for biological activity and DNA-drug interaction.
Rodriguez D, Quiros LM, Salas JA
[PMID: 14660589]J Biol Chem. 279 (2004) 8149-58
Elucidation of the glycosylation sequence of mithramycin biosynthesis: isolation of 3A-deolivosylpremithramycin B and its conversion to premithramycin B by glycosyltransferase MtmGII.
Nur-e-Alam M, Mendez C, Salas JA, Rohr J
[PMID: 15712316]Chembiochem. 6 (2005) 632-6
Characterization of kinetics and products of the Baeyer-Villiger oxygenase MtmOIV, the key enzyme of the biosynthetic pathway toward the natural product anticancer drug mithramycin from Streptomyces argillaceus.
Gibson M, Nur-e-alam M, Lipata F, Oliveira MA, Rohr J
[PMID: 16351075]J Am Chem Soc. 127 (2005) 17594-5
Crystallization and X-ray diffraction properties of Baeyer-Villiger monooxygenase MtmOIV from the mithramycin biosynthetic pathway in Streptomyces argillaceus.
Wang C, Gibson M, Rohr J, Oliveira MA
[PMID: 16511225]Acta Crystallogr Sect F Struct Biol Cryst Commun. 61 (2005) 1023-6
Novel GC-rich DNA-binding compound produced by a genetically engineered mutant of the mithramycin producer Streptomyces argillaceus exhibits improved transcriptional repressor activity: implications for cancer therapy.
Albertini V, Jain A, Vignati S, Napoli S, Rinaldi A, Kwee I, Nur-e-Alam M, Bergant J, Bertoni F, Carbone GM, Rohr J, Catapano CV
[PMID: 16571899]Nucleic Acids Res. 34 (2006) 1721-34
Premithramycinone G, an early shunt product of the mithramycin biosynthetic pathway accumulated upon inactivation of oxygenase MtmOII.
Abdelfattah MS, Rohr J
[PMID: 16856198]Angew Chem Int Ed Engl. 45 (2006) 5685-9
Crystal structure of Baeyer-Villiger monooxygenase MtmOIV, the key enzyme of the mithramycin biosynthetic pathway .
Beam MP, Bosserman MA, Noinaj N, Wehenkel M, Rohr J
[PMID: 19364090]Biochemistry. 48 (2009) 4476-87
Investigating Mithramycin deoxysugar biosynthesis: enzymatic total synthesis of TDP-D-olivose.
Wang G, Kharel MK, Pahari P, Rohr J
[PMID: 21960454]Chembiochem. 12 (2011) 2568-71
Cooperation of two bifunctional enzymes in the biosynthesis and attachment of deoxysugars of the antitumor antibiotic mithramycin.
Wang G, Pahari P, Kharel MK, Chen J, Zhu H, Van Lanen SG, Rohr J
[PMID: 22997042]Angew Chem Int Ed Engl. 51 (2012) 10638-42
Structural insight into MtmC, a bifunctional ketoreductase-methyltransferase involved in the assembly of the mithramycin trisaccharide chain.
Chen JM, Hou C, Wang G, Tsodikov OV, Rohr J
[PMID: 25587924]Biochemistry. 54 (2015) 2481-9
Expanding the Chemical Diversity of the Antitumoral Compound Mithramycin by Combinatorial Biosynthesis and Biocatalysis: The Quest for Mithralogs with Improved Therapeutic Window.
Mendez C, Gonzalez-Sabin J, Moris F, Salas JA
[PMID: 26393942]Planta Med. 81 (2015) 1326-38

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Compound nameGenomic
nucleotide
sequence
Nucleotide
sequences of the
coding regions
Translation of the
coding sequences
List of genes/ORFsGBK
Mithramycin
Genomic nucleotide sequence
43 KB
Nucleotide sequences of the coding regions
40 KB
Translation of the coding sequences
15 KB
List of genes/ORFs
5 KB

 

 
GenBank format
90 KB

close this sectionHistory

  • 2016-12-27[Update]
  • 2016-01-27[Update]
  • 2013-05-28[Release]