1887

Abstract

Tylosin is produced by via a combination of polyketide metabolism and synthesis of three deoxyhexose sugars, of which mycaminose is the first to be added to the polyketide aglycone, tylactone (protylonolide). Previously, disruption of the gene () encoding attachment of mycaminose to the aglycone unexpectedly abolished accumulation of the latter, raising the possibility of a link between polyketide metabolism and deoxyhexose biosynthesis in . However, at that time, it was not possible to eliminate an alternative explanation, namely, that downstream effects on the expression of other genes, not involved in mycaminose metabolism, might have contributed to this phenomenon. Here, it is shown that disruption of any of the four genes ( and ) specifically involved in mycaminose biosynthesis elicits a similar response, confirming that production of mycaminosyl-tylactone directly influences polyketide metabolism in . Under similar conditions, when mycaminose biosynthesis was specifically blocked by gene disruption, accumulation of tylactone could be restored by exogenous addition of glycosylated tylosin precursors. Moreover, certain other macrolides, not of the tylosin pathway, were also found to elicit qualitatively similar effects. Comparison of the structures of stimulatory macrolides will facilitate studies of the stimulatory mechanism.

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2001-04-01
2024-04-26
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References

  1. Baltz R. H., Seno E. T. 1988; Genetics of Streptomyces fradiae and tylosin biosynthesis. Annu Rev Microbiol 42:547–574 [CrossRef]
    [Google Scholar]
  2. Bate N., Cundliffe E. 1999; The mycinose-biosynthetic genes of Streptomyces fradiae , producer of tylosin. J Ind Microbiol Biotechnol 23:118–122 [CrossRef]
    [Google Scholar]
  3. Bate N., Butler A. R., Gandecha A. R., Cundliffe E. 1999; Multiple regulatory genes in the tylosin biosynthetic cluster of Streptomyces fradiae . Chem Biol 6:617–624 [CrossRef]
    [Google Scholar]
  4. Bate N., Butler A. R., Smith I. P., Cundliffe E. 2000; The mycarose-biosynthetic genes of Streptomyces fradiae , producer of tylosin. Microbiology 146:139–146
    [Google Scholar]
  5. Beckmann R. J., Cox K., Seno E. T. 1989; A cluster of tylosin biosynthetic genes is interrupted by a structurally unstable segment containing four repeated sequences. In Genetics and Molecular Biology of Industrial Microorganisms pp 176–186 Edited by Hershberger C. L., Queener S. W., Skatrud P. L. Washington, DC: American Society for Microbiology;
    [Google Scholar]
  6. Bibb M. J., White J., Ward J. M., Janssen G. R. 1994; The mRNA for the 23S rRNA methylase encoded by the ermE gene of Saccharopolyspora erythraea is translated in the absence of a conventional ribosome-binding site. Mol Microbiol 14:533–545 [CrossRef]
    [Google Scholar]
  7. Bierman M., Logan R., O’Brien K., Seno E. T., Rao R. N., Schoner B. E. 1992; Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene 116:43–49 [CrossRef]
    [Google Scholar]
  8. Blondelet-Rouault M.-H., Weiser J., Lebrihi A., Branny P., Pernodet J.-L. 1997; Antibiotic resistance cassettes derived from the Ω interposon for use in E. coli and Streptomyces . Gene 190:315–317 [CrossRef]
    [Google Scholar]
  9. Butler A. R., Bate N., Cundliffe E. 1999; Impact of thioesterase activity on tylosin biosynthesis in Streptomyces fradiae . Chem Biol 6:287–292 [CrossRef]
    [Google Scholar]
  10. Clark S. L. 1997 Analysis of the tylLM region of the Streptomyces fradiae chromosome PhD thesis University of Leicester;
    [Google Scholar]
  11. Cundliffe E. 1999; Organization and control of the tylosin-biosynthetic genes of Streptomyces fradiae . Actinomycetologica 13:68–75 [CrossRef]
    [Google Scholar]
  12. Fish S. A., Cundliffe E. 1997; Stimulation of polyketide metabolism in Streptomyces fradiae by tylosin and its glycosylated precursors. Microbiology 143:3871–3876 [CrossRef]
    [Google Scholar]
  13. Fishman S. E., Cox K., Larson J. L., Reynolds P. A., Seno E. T., Yeh W.-K., Van Frank R., Hershberger C. L. 1987; Cloning genes for the biosynthesis of a macrolide antibiotic. Proc Natl Acad Sci USA 84:8248–8252 [CrossRef]
    [Google Scholar]
  14. Fouces R., Mellado E., Dı́ez B., Barredo J. L. 1999; The tylosin biosynthetic cluster from Streptomyces fradiae : genetic organization of the left region. Microbiology 145:855–868 [CrossRef]
    [Google Scholar]
  15. Gandecha A. R., Cundliffe E. 1996; Molecular analysis of tlrD , an MLS resistance determinant from the tylosin producer, Streptomyces fradiae . Gene 180:173–176 [CrossRef]
    [Google Scholar]
  16. Gandecha A. R., Large S. L., Cundliffe E. 1997; Analysis of four tylosin biosynthetic genes from the tylLM region of the Streptomyces fradiae genome. Gene 184:197–203 [CrossRef]
    [Google Scholar]
  17. Janssen G. R., Bibb M. J. 1993; Derivatives of pUC18 that have Bgl II sites flanking a modified multiple cloning site and that retain the ability to identify recombinant clones by visual screening of Escherichia coli colonies. Gene 124:133–134 [CrossRef]
    [Google Scholar]
  18. Merson-Davies L. A., Cundliffe E. 1994; Analysis of five tylosin biosynthetic genes from the tylIBA region of the Streptomyces fradiae genome. Mol Microbiol 13:349–355 [CrossRef]
    [Google Scholar]
  19. Rosteck P. R. Jr, Reynolds P. A., Hershberger C. L. 1991; Homology between proteins controlling Streptomyces fradiae tylosin resistance and ATP-binding transport. Gene 102:27–32 [CrossRef]
    [Google Scholar]
  20. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual , 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  21. Szoke P. A., Reynolds P. A., Kreuzman A. J., Yeh W.-K., Becker G. W., Hershberger C. L, Rosteck P. R. Jr 1989; Sequence analysis of tylosin biosynthetic genes. In Abstracts of Posters of the Annual Meeting of the American Society for Microbiology New Orleans: Abstract number H10;
    [Google Scholar]
  22. Wilson V. T. W., Cundliffe E. 1998; Characterization and targeted disruption of a glycosyltransferase gene in the tylosin producer, Streptomyces fradiae . Gene 214:95–100 [CrossRef]
    [Google Scholar]
  23. Wilson V. T. W., Cundliffe E. 1999; Molecular analysis of tlrB , an antibiotic-resistance gene from tylosin-producing Streptomyces fradiae , and discovery of a novel resistance mechanism. J Antibiot 52:288–296 [CrossRef]
    [Google Scholar]
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