SCO3023

Summary

Gene Symbol: SCO3023
Description: adenosylhomocysteinase
Alias: SCE34.04c, sahH
Species: Streptomyces coelicolor A3(2)

Top Publications

  1. Remsing L, Gonz lez A, Nur E Alam M, Fern ndez Lozano M, Bra a A, Rix U, et al. 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. 2003;125:5745-53 pubmed publisher
    ..The major product, MTM-SK, was tested in vitro against a variety of human cancer cell lines, as well as in an in vitro toxicity assay, and showed an improved therapeutic index, in comparison to the parent drug, MTM...
  2. Fern ndez E, Weissbach U, S nchez Reillo C, Bra a A, M ndez C, Rohr J, et al. Identification of two genes from Streptomyces argillaceus encoding glycosyltransferases involved in transfer of a disaccharide during biosynthesis of the antitumor drug mithramycin. J Bacteriol. 1998;180:4929-37 pubmed
  3. Prado L, Fern ndez E, Weissbach U, Blanco G, Quir s L, Bra a A, et al. Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin. Chem Biol. 1999;6:19-30 pubmed
    ..The following decarboxylation and ketoreduction steps lead to mithramycin. Opening of the fourth ring represents one of the last steps in mithramycin biosynthesis...
  4. Garcia Bernardo J, Bra a A, M ndez C, Salas J. 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. 2000;186:61-5 pubmed
    ..It is proposed that mtrX and mtrY could code for a secondary defense mechanism and a mithramycin regulatory element, respectively...
  5. Blanco G, Fu H, Mendez C, Khosla C, Salas J. Deciphering the biosynthetic origin of the aglycone of the aureolic acid group of anti-tumor agents. Chem Biol. 1996;3:193-6 pubmed
    ..The final steps in the aglycone biosynthetic pathway presumably involve decarboxylation and oxidative cleavage between C-18 and C-19, followed by additional oxidation, reduction, and methylation reactions. ..
  6. Nur E Alam M, M ndez C, Salas J, Rohr J. Elucidation of the glycosylation sequence of mithramycin biosynthesis: isolation of 3A-deolivosylpremithramycin B and its conversion to premithramycin B by glycosyltransferase MtmGII. Chembiochem. 2005;6:632-6 pubmed publisher
  7. Fernandez E, Lombo F, Mendez C, Salas J. An ABC transporter is essential for resistance to the antitumor agent mithramycin in the producer Streptomyces argillaceus. Mol Gen Genet. 1996;251:692-8 pubmed
    ..argillaceus...
  8. Remsing L, Garcia Bernardo J, Gonzalez A, K nzel E, Rix U, Bra a A, et al. 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 nove. J Am Chem Soc. 2002;124:1606-14 pubmed
    ..The same is true for glycosyltransferases MtmGI and MtmGII, both of which partake in the formation and attachment of the A-B disaccharide in mithramycin...
  9. Trefzer A, Blanco G, Remsing L, K nzel E, Rix U, Lipata F, et al. Rationally designed glycosylated premithramycins: hybrid aromatic polyketides using genes from three different biosynthetic pathways. J Am Chem Soc. 2002;124:6056-62 pubmed
    ..The successful combination of two glycosyltransferases in the latter experiment proves that the design of saccharide side chains by combinatorial biosynthetic methods is possible...

More Information

Publications16

  1. Rodriguez D, Quiros L, Brana A, Salas J. Purification and characterization of a monooxygenase involved in the biosynthetic pathway of the antitumor drug mithramycin. J Bacteriol. 2003;185:3962-5 pubmed
    ..One of the reaction products showed important biological activity, thus highlighting the importance of the cleavage of the fourth ring of the aglycon for biological activity. ..
  2. Wohlert S, K nzel E, Machinek R, M ndez C, Salas J, Rohr J. The structure of mithramycin reinvestigated. J Nat Prod. 1999;62:119-21 pubmed publisher
    ..The structure elucidation was carried out with mithramycin decaacetate (4) using 2D NMR methods, including TOCSY, HMBC, and HSQC experiments. The work resulted in structure 3being confirmed for mithramycin...
  3. Lozano M, Remsing L, Quir s L, Bra a A, Fern ndez E, S nchez C, et al. Characterization of two polyketide methyltransferases involved in the biosynthesis of the antitumor drug mithramycin by Streptomyces argillaceus. J Biol Chem. 2000;275:3065-74 pubmed
    ..A pathway is proposed for the last steps in the biosynthesis of mithramycin involving these methylation events...
  4. Blanco G, Fern ndez E, Fern ndez M, Bra a A, Weissbach U, K nzel E, et al. Characterization of two glycosyltransferases involved in early glycosylation steps during biosynthesis of the antitumor polyketide mithramycin by Streptomyces argillaceus. Mol Gen Genet. 2000;262:991-1000 pubmed
    ..These experiments demonstrate that the glycosyltransferases MtmGIV and MtmGIII catalyze the first two glycosylation steps in mithramycin biosynthesis. A model is proposed for the glycosylation steps in mithramycin biosynthesis...
  5. Lombó -, Künzel -, Prado -, Braña -, Bindseil -, Frevert -, et al. 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. 2000;39:796-799 pubmed
  6. Rodr guez D, Quir s L, Salas J. MtmMII-mediated C-methylation during biosynthesis of the antitumor drug mithramycin is essential for biological activity and DNA-drug interaction. J Biol Chem. 2004;279:8149-58 pubmed publisher
  7. Kantola J, Blanco G, Hautala A, Kunnari T, Hakala J, Mendez C, et al. Folding of the polyketide chain is not dictated by minimal polyketide synthase in the biosynthesis of mithramycin and anthracycline. Chem Biol. 1997;4:751-5 pubmed
    ..These experiments clearly support the involvement of ketoreductase and a cyclase in the regiospecific cyclization of the biosynthetic pathway for aromatic polyketides. ..