1887

Abstract

A DNA segment cloned from ATCC 25489 close to a region that hybridized to a probe containing part of the actinorhodin polyketide synthase caused ATCC 31615 to produce new anthracyclines. When transformed with certain sub-clones of this segment, the host produced glycosides of β-rhodomycinone,β-rhodomycinone, 10-demethoxycarbonylaklavinone and 11-deoxy-β-rhodomycinone in addition to those of aklavinone, the natural anthracyclines of . The first two compounds are products and the other two are novel compounds that conceptually are structural hybrids between and products. Three glycosides of one of the novel aglycones, 11-deoxy-β-rhodomycinone, were purified and found to possess cytotoxic activity against L1210 mouse leukaemia cells. Separate regions of the cloned DNA are responsible for modification of the host product at the 10- and 11-positions.

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1994-06-01
2024-04-26
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References

  1. Baltz R.H. 1986; Mutagenesis in Streptomjces. In Manual of Industrial Microbiology and Biotechnology pp. 184–90 Edited by Demain A. L., Solomon N. A. . Washington, DC: American Society for Microbiology;
    [Google Scholar]
  2. Bolivar F., Rodriguez R. L., Greene P. J., Betlach M. C., Heyneker H. L., Boyer H. W., Crosa J. H., Falkow S. 1977; Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. Gene 2:95–113
    [Google Scholar]
  3. Brockmann H., Niemeyer J., Rode W. 1965; Rhodomycine, IX, Antibiotica aus Actinomyceten, III: yS-iso-rhodomycinon. Chem Ber 98:3145–3152
    [Google Scholar]
  4. Eckardt K., Wagner C. 1988; Biosynthesis of anthracyclinones. J Basic Microbiol 28:137–144
    [Google Scholar]
  5. Feinberg A.P., Vogelstein B. 1983; A technique for radio-labeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13
    [Google Scholar]
  6. Feinberg A.P., Vogelstein B. 1984; Addendum: a technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 137:266–267
    [Google Scholar]
  7. Frischauf A.M., Lehrach H., Poustka A., Murray N. 1983; Lambda replacement vectors carrying polylinker sequences. J Mol Biol 170:827–842
    [Google Scholar]
  8. Fujiwara A., Hoshino T., Tazoe M. 1980 Process to produce aclacinomycins A and B US Patent 4375511 Published 1 March 1983, priority 27 October 1980.
    [Google Scholar]
  9. Henikoff S. 1984; Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene 28:351–359
    [Google Scholar]
  10. Henikoff S. 1987; Unidirectional digestion with exonuclease III in DNA sequence analysis. Methods Ensymol 155:156–165
    [Google Scholar]
  11. Hopwood D.A. 1981; Future possibilities for the discovery of new antibiotics by genetic engineering. In Beta-Lactam Antibiotics pp. 585–598 Edited by Salton M. R. J., Shockman G. D. . New York: Academic Press;
    [Google Scholar]
  12. Hopwood D. A., Bibb M. J., Chater K. F., Kieser T., Bruton C. J., Kieser H. M., Lydiate D. J., Smith C. P., Ward J.M., Schrempf H. 1985a Genetic Manipulation of Streptomyces: A Laboratory Manual. Norwich: John Innes Foundation;
    [Google Scholar]
  13. Hopwood D. A., Malpartida F., Kieser H. M., Ikeda H., Duncan J., Fujii I., Rudd B, Floss A. M. H. G., Omura S. 1985b; Production of‘hybrid’ antibiotics by genetic engineering. Nature 314:642–644
    [Google Scholar]
  14. Hoshino Y., Sekine Y., Fujiwara A. 1983; Microbial conversion of aclacinomycin B to aclacinomycin A. J Antibiot 36:1458–1462
    [Google Scholar]
  15. Jones G.H., Hopwood D. A. 1984; Activation of phenoxa- zinone synthase expression in Streptomyces lividans by cloned sequences from Streptomyces antibioticus. J Biol Chem 259:14158–14164
    [Google Scholar]
  16. Kaslow D.C. 1986; A rapid biochemical method for purifying λ- DNA from phage lysates. Nucleic Acids Res 14:6767
    [Google Scholar]
  17. Kieser T. 1984; Factors affecting the isolation of CCC DNA from Streptomyces lividans and Escherichia coli. Plasmid 12:19–36
    [Google Scholar]
  18. Malpartida F., Hallam S. E., Kieser H. M., Motamedi H., Hutchinson C. R., Butler M. J., Sugden D. A., Warren M., McKillop C., Bailey C. R., Humphreys G. O., Hopwood D. A. 1994; Homology between Streptomyces genes coding for synthesis of different polyketides and its use to clone antibiotic biosynthetic genes. Nature 325:818–821
    [Google Scholar]
  19. Maniatis T., Fritsch E. F., Sambrook J. 1982 Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  20. Matsuzawa Y., Oki T., Takeuchi T., Umezawa H. 1981; Structure-activity relationships of anthracyclines relative to cytotoxicity and effects on macromolecular synthesis in LI 210 leukemia cells. J Antibiot 34:1596–1606
    [Google Scholar]
  21. Oki T. 1984; Recent developments in the process improvement of production of antitumor anthracycline antibiotics. Adv Biotechnol Processes 3:163–196
    [Google Scholar]
  22. Oki T., Matsuzawa Y., Yoshimoto A., Numata K., Kitamura I., Hori S., Takamatsu A., Umezawa H., Ishizuka M., Naganawa H, Suda H., Hamada M., Takeuchi T. 1975; New antitumor antibiotics, aclacinomycins A and B. J Antibiot 28:830–834
    [Google Scholar]
  23. Otake IM, Tatsuta K., Hayakawa Y., Otsuki N. 1985 Anthra-cycline compounds and antitumor agents containing them. Japanese Patent 62-81398. Application date 3 October 1985
    [Google Scholar]
  24. Raleigh E. A., Murray N. E., Revel H., Blumenthal R. M., Westaway D., Reith A. D., Rigby P. W. J., Elhai J., Hanahan D. 1995; Mcr A and Mcr B restriction phenotypes of some E. coli strains and implications for gene cloning. Nucleic Acids Res 16:1563–1575
    [Google Scholar]
  25. Rosenberg S.M. 1987; Improved in vitro packaging of lambda DNA. Methods Ensymol 153:95–103
    [Google Scholar]
  26. Rosenberg S. M., Stahl M. M., Kobayashi I., Stahl F. W. 1985; Improved in vitro packaging of coliphage lambda DNA: a one- strain system free from endogenous phage. Gene 38:165–175
    [Google Scholar]
  27. Shirling E.B., Gottlieb D. 1969; Cooperative description of type cultures of Streptomyces. IV. Species descriptions from the second, third and fourth studies. Int J Syst Bacteriol 19:391–512
    [Google Scholar]
  28. Stutzman-Engwall K.J., Hutchinson C. R. 1989; Multigene families for anthracycline antibiotic production in Streptomyces peucetius. Proc Natl Acad Sci USA 86:3135–3139
    [Google Scholar]
  29. Stutzman-Engwall K. J., Otten S. L., Hutchinson C. R. 1992; Regulation of secondary metabolism in Streptomyces spp. and overproduction of daunorubicin in Streptomyces peucetius. J Bacteriol 174:144–154
    [Google Scholar]
  30. Tanaka H., Yoshioka T., Shimauchi Y., Matsuzawa Y., Oki T., Inui T. 1980; Chemical modification of anthracycline antibiotics. I Demethoxycarbonylation, 10-epimerization and 4-O-methylation of aclacinomycin A. Antibiot 33:1323–1330
    [Google Scholar]
  31. Ward J. M., Janssen G. R., Kieser T., Bibb M. J., Buttner M. J., Bibb M. J. 1986; Construction and characterization of a series of multi-copy promoter-probe plasmid vectors for Streptomyces using the aminoglycoside phosphotransferase from Tn5as indicator. Mol and Gen Genet 203:468–478
    [Google Scholar]
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