1887

Abstract

sp. strain C5, an organism that normally produces baumycins, daunomycin and ε-rhodomycinone, was treaed with -methyl-′-nitro--nitrosoguanidine (NTG). Mutants blocked at arious points in daunomycin and baumycin production were isolated by screening for altered pigmentation and absnce of bioactivity against . Examination of the mutants by thin-layer chromatography of their accumulated anthracycline metabolites, by cosynthesis assays, and by extract feeding experiments allowed a classification into six groups. Theses were: , strains that accumulated no anthracyclines but with other blocked mutants cosynthesized anthracyclines (polyketide-synthase-minus mutants); , regulatory mutants that, either alone or mixed with other blocked mutants, accumulated no anthracyclines; , mutants that accumulated aklanonic acid; , mutants that accumulated maggiemycin; , mutants that accumulated aklavinone; and , mutants that accumulated only ε-rhodomycinone. Mutant SC5-24 (), which accumulated that shunt product maggiemycin, was re-mutagenized with NTG to obtain blocked mutants in preceding biosynthetic steps; the three grops of double mutants obtained accumulated aklanonic acid (), aklanonic acid methyl ester () and akalviketone ().

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-136-9-1877
1990-09-01
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/micro/136/9/mic-136-9-1877.html?itemId=/content/journal/micro/10.1099/00221287-136-9-1877&mimeType=html&fmt=ahah

References

  1. Arcamone F. 1984; Antitumor anthracyclines: recent developments. Medical Research Reviews 4:153–188
    [Google Scholar]
  2. Bibb M. J., Biro S., Motamedi H., Collins J. F., Hutchinson C. R. 1989; Analysis of the nucleotide sequence of the Streptomyces glaucescens tcmI genes provides key information about the enzymology of polyketide biosynthesis. EMBO Journal 8:2727–2736
    [Google Scholar]
  3. Blumauerová M., Královková E., Koštalek Z., Vanek Z. 1979; Intra- and interspecific cosynthetic activity of mutants of Streptomyces coeruleorubidus and Streptomyces galilaeus impaired in the biosynthesis of anthracyclines. Folia Microbiologia 24:128–135
    [Google Scholar]
  4. Cassinelli G., Rivola G., Ruggieri D., Arcamone F., Grein A., Merli S., Spalla C., Casazza A. M., Dimarco A., Pratesi G. 1982; New anthracycline glycosides: 4-O-demethyl-11-deoxydaun- orubicin and analogues from Streptomyces peucetius var. aureus. Journal of Antibiotics 35:176–183
    [Google Scholar]
  5. Connors N. C., Bartel P. L., Strohl W. R. 1990a; Biosynthesis of anthracyclines: enzymic conversion of aklanonic acid to aklavinone and ε-rhodomycinone by anthracycline-producing streptomycetes. Journal of General Microbiology 136:1887–1894
    [Google Scholar]
  6. Connors N. C., Bartel P. L., Strohl W. R. 1990b; Biosynthesis of anthracyclines: carminomycin 4-O-methyltransferase, the terminal enzymic step in the formation of daunomycin. Journal of General Microbiology 136:1895–1898
    [Google Scholar]
  7. Dekleva M. L., Titus J. A., Strohl W. R. 1985; Nutrient effects on anthracycline production by Streptomyces peucetius in a defined medium. Canadian Journal of Microbiology 31:287–294
    [Google Scholar]
  8. Delić V., Pigac J., Sermonti G. 1969; Detection and study of cosynthesis of tetracycline antibiotics by an agar method. Journal of General Microbiology 55:103–108
    [Google Scholar]
  9. Delić V., Hopwood D. A., Friend E. 1970; Mutagenesis by N-methyl-N′-nitro-N-nitrosoguanidine (NTG) in Streptomyces coelicolor. Mutation Research 9:167–182
    [Google Scholar]
  10. Eckardt K., Wagner C. 1988; Biosynthesis of anthracyclinones. Journal of Basic Microbiology 28:137–144
    [Google Scholar]
  11. Eckardt K., Tresselt D., Schumann G., Ihn W., Wagner C. 1985; Isolation and chemical structure of aklanonic acid, an early intermediate in the biosynthesis of anthracyclines. Journal of Antibiotics 38:1034–1039
    [Google Scholar]
  12. Eckardt K., Schumann G., Tresselt D., Ihn W. 1988; Biosynthesis of anthracyclinones: isolation of a new early cyclization product aklaviketone. Journal of Antibiotics 41:788–793
    [Google Scholar]
  13. Fujiwara A., Hoshino T. 1983; Anthracycline antibiotics. CRC Critical Reviews in Biotechnology 3:133–157
    [Google Scholar]
  14. Hallam S. E., Malpartida F., Hopwood D. A. 1988; Nucleotide sequence, transcription and deduced function of a gene involved in polyketide antibiotic synthesis in Streptomyces coelicolor. Gene 74:305–320
    [Google Scholar]
  15. Hopwood D. A., Bibb M. J., Chater K. F., Kieser T., Bruton J. J., Kieser H. M., Lydiate D. J., Smith C. P., Ward J. M., Schrempf H. 1985 Genetic Manipulation of Streptomyces, a Laboratory Manual Norwich: John Innes Foundation;
    [Google Scholar]
  16. Ihn W., Wagner C., Fleck W. F., Tresselt D., Eritt I., Sedmera P. 1984; Leukaemomycin-geblockte Mutanten des Streptomyces griseus und ihre Pigmente. II. Neue 7-Hydroxy-bisanhydro-rhodomycinone aus der Mutane ZIMET 41707/1P. Zeitschrift für Allgemeine Mikrobiologie 24:525–532
    [Google Scholar]
  17. Jizba J. V., Sedmera P., Vokoun J., Blumauerová M., Vanąk Z. 1980; Naphthacenequinone derivatives from a mutant strain of Streptomyces coeruleorubidus. Collection of Czechoslovak Chemical Communications 45:764–771
    [Google Scholar]
  18. Královková E., Sedmera P., Vokoun J., Vaněk Z. 1980; Anthraquinones related to anthracyclinones from the mutant strain Streptomyces galilaeus, J-14. Collection of Czechoslovak Chemical Communications 45:2558–2565
    [Google Scholar]
  19. McGuire J. C., Glotfelty G., White R. J. 1980a; Use of cerulenin in strain improvement of the daunorubicin fermentation. FEMS Microbiology Letters 9:141–143
    [Google Scholar]
  20. McGuire J. C., Thomas M. C., Pandey R., Toussaint M., White R. J. 1980b; Biosynthesis of daunorubicin glucosides: analysis with blocked mutants. Advances in Biotechnology 3:117–122
    [Google Scholar]
  21. McGuire J. C., Thomas M. C., Stroshane R. M., Hamilton B. K., White R. J. 1980c; Biosynthesis of daunorubicin glycosides: role of ε-rhodomycinone. Antimicrobial Agents and Chemotherapy 18:454–464
    [Google Scholar]
  22. Motamedi H., Wendt-Pienkowski E., Hutchinson C. R. 1986; Isolation of tetracenomycin C-nonproducing Streptomyces glaucescens mutants. Journal of Bacteriology 167:575–580
    [Google Scholar]
  23. Oki T., Kitamura I., Matsuzawa Y., Shibamoto N., Ogasawara T., Yoshimoto A., Inui T. 1979; Antitumor anthracycline antibiotics, aclacinomycin A and analogs. Journal of Antibiotics 32:801–819
    [Google Scholar]
  24. Pandey R. C., Toussaint M. W., McGuire J. C., Thomas M. C. 1989; Maggiemycin and anhydromaggiemycin: two novel anthracyclinone antibiotics. Journal of Antibiotics 42:1567–1577
    [Google Scholar]
  25. Rudd B. A. M., Hopwood D. A. 1979; Genetics of actinorhodin biosynthesis by Streptomyces coelicolor A3(2). Journal of General Microbiology 114:35–43
    [Google Scholar]
  26. Schlegel B., Stengel C., Schumann G., Prauser H., Eckardt K. 1987; Aklanonic acid-producing mutants of Streptomyces galilaeus and Streptomyces peucetius var. caesius. Journal of Basic Microbiology 27:107–111
    [Google Scholar]
  27. Schumann G., Stengel C., Eckardt K., Ihn W. 1986; Biotransformation of aklanonic acid by blocked mutants of anthracycline-producing strains of Streptomyces galilaeus and Streptomyces peucetius. Journal of Basic Microbiology 26:249–255
    [Google Scholar]
  28. Sherman D. H., Malpartida F., Bibb M. J., Kieser H. M., Bibb M. J., Hopwood D. A. 1989; Structure and deduced function of the granaticin-producing polyketide synthase gene cluster of Streptomyces violaceoruber Tü22. EMBO Journal 8:2717–2725
    [Google Scholar]
  29. Strauss D., Fleck W. F. 1975; Leukaemomycin, an antibiotic with antitumor activity. II. Isolation and identification. Zeitschrift für Allgemeine Mikrobiologie 15:615–623
    [Google Scholar]
  30. Strohl W. R., Bartel P. L., Connors N. C., Zhu C. -B., Dosch D. C., Beale J. M. Jr Stutzman-Engwall K., Otten S. L., Hutchinson C. R. 1989; Biosynthesis of natural and hybrid polyketides by anthracycline-producing streptomycetes. In Genetics and Molecular Biology of Industrial Microorganisms pp. 68–84 Hershberger C. L., Queener S. W., Hegeman G. Edited by Washington, DC: American Society for Microbiology;
    [Google Scholar]
  31. Stutzman-Engwall K. J., Hutchinson C. R. 1989; Multigene families for anthracycline antibiotic production in Streptomyces peucetius. Proceedings of the National Academic of Sciences of the United States of America 86:3135–3139
    [Google Scholar]
  32. Thomas R., Williams D. J. 1983; Oxytetracycline biosynthesis: mode of incorporation of [1-13C]- and [1,2-13C2]-acetate. Journal of the Chemical Society, Chemical Communications128–130
    [Google Scholar]
  33. Tobe H., Yoshimoto A., Ishikura T., Naganawa H., Takeuchi T., Umezawa H. 1982; New anthracyclinone metabolites from two blocked mutants of Streptomyces galilaeus MA144-M1. Journal of Antibiotics 35:1641–1645
    [Google Scholar]
  34. Wagner C., Stengel C., Eritt I., Schumann G., Fleck W. F. 1981; Leukaemomycin-geblockte Mutanten des Streptomyces griseus und ihre Pigmente. Zeitschrift für Allgemeine Mikrobiologie 21:751–760
    [Google Scholar]
  35. Wagner C., Eckardt K., Schumann G., Ihn W., Tresselt D. 1984; Microbial transformation of aklanonic acid, a potential early intermediate in the biosynthesis of anthracyclines. Journal of Antibiotics 37:691–692
    [Google Scholar]
  36. Wagner C., Eckardt K., Tresselt D., Ihn W., Schumann G., Fleck W. F. 1985; Leukaemomycin-geblockte Mutanten des Streptomyces griseus und ihre Pigmente. III. 11-Desoxydaunomycinonderivate aus der Mutante ZIMET 43 699/G44. Journal of Basic Microbiology 25:687–693
    [Google Scholar]
  37. Yoshimoto A., Oki T., Umezawa H. 1980; Biosynthesis of daunomycinone from aklavinone and ε-rhodomycinone. Journal of Antibiotics 33:1199–1201
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-136-9-1877
Loading
/content/journal/micro/10.1099/00221287-136-9-1877
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error