Two multifunctional peptide synthetases and an O-methyltransferase are involved in the biosynthesis of the DNA-binding antibiotic and antitumour agent saframycin Mx1 from Myxococcus xanthus

Microbiology

Volumn 142, Issue 4, 1996, Pages 741-746

  Pospiech, Andreas ^a   Bietenhader, Jürg ^a   Schupp, Thomas ^a  

^a CIBA GEIGY LTD   (Switzerland)

Author keywords

Antibiotic; Myxococcus xanthus; O methyltransferase; Peptide synthetase; Saframycin Mx1

Indexed keywords

ANTIBIOTIC AGENT; ANTINEOPLASTIC ANTIBIOTIC; METHYLTRANSFERASE; PEPTIDE SYNTHASE; SAFRAMYCIN;

ARTICLE; CELL SECRETION; DNA BINDING; DNA SEQUENCE; DRUG SYNTHESIS; MYXOCOCCALES; NONHUMAN; OPEN READING FRAME; PRIORITY JOURNAL; PROTEIN DOMAIN;

MYXOCOCCALES; MYXOCOCCUS XANTHUS;

EID: 0029996171     PISSN: 13500872     EISSN: None     Source Type: Journal    
DOI: 10.1099/00221287-142-4-741     Document Type: Article

References (38)

1. Arai, T., Takahashi, K. & Kubo, A. (1977). New antibiotics, saframycins A, B, C, D, and E. J Antibiot 30, 1015-1018.
2. Arai, T., Takahashi, K., Ishiguro, K. & Mikami, Y. (1980). Antitumor antibiotics, saframycin A and C. Gann 71, 790-796.
3. - mutation in Anabaena sp. strain PCC7120 implicates a secondary metabolite in the regulation of hererocyst spacing. J Bacteriol 176, 2282-2292.
4. Cosmina, P., Rodriguez, F., de Ferre, F., Grandi, G., Perego, M., Venema, G. & van Sinderen, D. (1993). Sequence and analysis of the genetic locus responsible for surfactin synthesis in Bacillus subtilis. Mol Microbiol 8, 821-831.
5. Devereux, J., Haeberli, P. & Smithies, O. (1984). A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 12, 387-395.
6. Donadio, S. & Katz, L. (1992). Organization of the enzymatic domains in the multifunctional polyketide synthase involved in erythromycin formation in Saccharopolyspora erythraea. Gene 111, 51-60.
7. D'Souza, C., Nakanno, M. M., Corbell, N. & Zuber, P. (1993). Aminoacylation site mutations in amino acid-activating domains of surfactin synthetase: effects on surfactin production and competence development in Bacillus subtilis. J Bacteriol 175, 3502-3510.
8. Gocht, M. & Marahiel, M. A. (1994). Analysis of core sequences in the D-Phe activating domain of the multifunctional peptide synthetase TycA by site-directed mutagenesis. J Bacteriol 176, 2654-2662.
9. Hara, O. & Hutchinson, C. R. (1992). A macrolide 3-O-acyltransferase gene from the midecamycin-producing species Streptomyces mycarofaciens. J Bacteriol 174, 5141-5144.
10. Hori, K., Yamamoto, Y., Minetoki, T., Kurotsu, T., Kanda, M., Miura, S., Okamura, K., Furujama, J. & Saito, Y. (1989). Molecular cloning and nucleotide sequence of the gramicidin S synthetase 1 gene. J Biochem 106, 639-645.
11. Irschick, H., Trowitzsch-Kienast, W., Gerth, K., Höfle, G. & Reichenbach, H. (1988). Saframycin Mx1, a new natural saframycin isolated from a myxobacterium. J Antibiot 41, 993-998.
12. Ishiguro, K., Sakiyama, S., Takahashi, K. & Arai, K. (1978). Mode of action of saframycin A, a novel heterocyclic quinone antibiotic. Inhibition of RNA synthesis in vivo and in vitro. Biochemistry 17, 2545-2550.
13. 14C]-cyanide. J Biol Chem 256, 2162-2167.
14. Kagan, R. M. & Clarke, S. (1994). Widespread occurrence of three sequence motifs in diverse S-adenosylmethione-dependent methyltransferases suggests a common structure for these enzymes. Arch Biochem Biophys 310, 417-427.
15. Kishi, K., Yazawa, K., Takahashi, K., Maeda, A. & Arai, K. (1984). Structure-activity relationships of saframycins. J.Antibiot 37, 847-852.
16. Kleinkauf, H. & von Döhren, H. (1990). Nonribosomal biosynthesis of peptide antibiotics. Eur J Biochem 192, 1-15.
17. Lown, J. W. , Joshua, A. V. & Lee, J. S. (1982). Molecular mechanisms of binding and single-strand scission of desoxyribonucleic acid by the antitumor antibiotics saframycin A and C. Biochemistry 21, 419-428.
18. Marahiel, M. A. (1992). Multidomain enzymes involved in peptide synthesis. FEBS Lett 307, 40-43.
19. Morris, M. E. & Jinks-Robertson, S. (1991). Nucleotide sequence of the LYS2 gene of Saccharomyces cerevisiae: homology to Bacillus brevis tyrocidine synthetase 1. Gene 98, 141-145.
20. Pavela-Vrancic, M., Pfeifer, E., van Liempt, H., Schäfer, H.-J., von Döhren, H. & Kleinkauf, H. (1994a). ATP-binding in peptide synthetases: determination of contact sites of the adenine moiety by photoaffinity labeling of tyrocidine synthetase I with 2-azidoadenosine triphosphate. Biochemistry 33, 6276-6283.
21. Pavela-Vrancic, M., Pfeifer, E., Schröder, W., von Döhren, H. & Kleinkauf, H. (1994b). Identification of the ATP-binding site in tyrocidine synthetase I by selective modification with fluorescein 5′-isothiocyanate. J Biol Chem 169, 14962-14966.
22. Pospiech, A., Cluzel, B., Bietenhader, J. & Schupp, T. (1995). A new Myxococcus xanthus gene cluster for the biosynthesis of the antibiotic saframycin Mx1 encoding a peptide synthetase. Microbiology 141, 1793-1803.
23. Reichenbach, H., Gerth, K., Irschik, H., Kunze, B. & Höfle, G. (1988). Myxobacteria: a source of new antibiotics. Trends Biotechnol 6, 115-121.
24. Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning, a Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
25. Sanger, F., Nicklen, S. & Coulson, A. R. (1977). DNA sequencing with chain terminating inhibitors. Proc Natl Acad Sci USA 74, 5463-5467.
26. Schlumbohm, W., Stein, T., Ullrich, C., Vater, J., Krause, M., Marahiel, M. A., Kruft, V. & Wittmann-Liebhold, B. (1991). An active serine is involved in covalent substrate amino acid binding at each reaction center of gramicidin S synthetase. J Biol Chem 266, 23135-23141.
27. Schmitt, D., Pakusch, A. E. & Matern, U. (1991). Molecular cloning, induction, and taxonomic distribution of caffeoyl-CoA-3-O-methyltransferase, an enzyme involved in disease resistance. J Biol Chem 266, 17416-17423.
28. Simon, R., O'Connell, M., Labes, M. & Pühler, A. (1986). Plasmid vectors for the genetic analysis and manipulation of rhizobia and other Gram-negative bacteria. Methods Enzymol 118, 643-659.
29. Simon, R., Priefer, U. & Pühler, A. (1983). A broad host range mobilization system for in vivo genetic engineering: transposon mutagenesis in gram negative bacteria. Bio/Technology 1, 784-791.
30. Stachelhaus, T. & Marahiel, M. A. (1995). Modular structure of genes encoding multifunctional peptide synthetases required for non-ribosomal peptide synthesis. FEMS Microbiol Lett 125, 3-14.
31. Stachelhaus, T., Schneider, A. & Marahiel, M. A. (1995). Rational design of novel peptide antbiotics by targeted replacement of bacterial and fungal domains. Science 269, 69-72.
32. Stein, T., Vater, J., Kruft, V., Wittmann-Liebold, B., Franke, P., Panico, M., Dowell, R. M. & Morris, H. R. (1994). Detection of 4′-phosphopantetheine at the thioester binding site for L-valine of gramicidin S synthetase 2. FEBS Lett 340, 39-44.
33. Tohika, K., Hori, K., Kurotzu, T., Kanda, M. & Saito, Y. (1993). Effect of single base substitutions at glycine-870 codon of gramicidin S synthetase 2 gene on proline activation. J Biochem 114, 522-527.
34. Trowitzsch-Kienast, W., Irschick, H., Reichenbach, H., Wray, V. & Höfle, G. (1988). Isolierung und Strukturaufklärung der Saframycine Mx1 und Mx2, neue antitumor-aktive Antibiotika aus Myxococcus xanthus. Liebigs Ann Chem 475-481.
35. Turgay, K., Krause, M. & Marahiel, M. A. (1992). Four homologous domains in the primary structure of GrsB are related to domains in a superfamily of adenylate-forming enzymes. Mol Microbiol 6, 529-546.
36. Vollenbroich, D., Kluge, B., D'Souza, C., Zuber, P. & Vater, J. (1993). Analysis of a mutant amino acid-activating domain of surfactin synthetase bearing a serine-to-alanine substitution at the site of carboxylthioester formation. FEBS Lett 325, 220-224.
37. Weber, J. M., Schoner, B. & Losick, R. (1989). Identification of a gene required for the terminal step in erythromycin A biosynthesis in Saccharopolyspora erythraea. Gene 75, 235-241.
38. Weckermann, R. W., Fürbaß, R. & Marahiel, M. A. (1988). Complete nucleotide sequence of the tycA gene coding the tyrocidine I synthetase from Bacillus brevis. Nucleic Acids Res 16, 11841.