1887

Abstract

The region of the genome was sequenced, revealing an incomplete set of five genes encoding all-but-one of the enzymes involved in the biosynthesis of mycarose. The latter is a 6-deoxyhexose sugar required during production of the macrolide antibiotic, tylosin. The missing mycarose-biosynthetic gene, , was found about 50 kb distant from its functional partners, on the other side of the (polyketide synthase) gene complex. Mutational analysis, involving targeted gene transplacement, was employed to confirm the functions of specific genes, including . Particularly interesting was the similarity between the tylosin-biosynthetic mycarosyltransferase enzyme, TylCV, and proteins of the macrolide glycosyltransferase (MGT) family that inactivate macrolides via glycosylation of attached sugar residues and are involved in resistance and/or antibiotic efflux. The arrangement of genes within the ‘mycarose cluster’ would allow their expression as two short operons with divergent, and perhaps co-regulated, promoters. Whether displacement of relative to the other genes provides additional regulatory opportunities remains to be established.

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2000-01-01
2022-01-29
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References

  1. Baltz R. H., Seno E. T. 1981; Properties of Streptomyces fradiae mutants blocked in biosynthesis of the macrolide antibiotic tylosin. Antimicrob Agents Chemother 20:214–225 [CrossRef]
    [Google Scholar]
  2. Baltz R. H., Seno E. T. 1988; Genetics of Streptomyces fradiae and tylosin biosynthesis. Annu Rev Microbiol 42:547–574 [CrossRef]
    [Google Scholar]
  3. Baltz R. H., Seno E. T., Stonesifer J., Wild G. M. 1983; Biosynthesis of the macrolide antibiotic tylosin. A preferred pathway from tylactone to tylosin. J Antibiot 36:131–141 [CrossRef]
    [Google Scholar]
  4. 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]
  5. 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]
  6. 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. 176–186Edited by Hershberger C. L., Queener S. W., Skatrud P. L. Washington, DC: American Society for Microbiology;
    [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. Dickens M. L., Ye J., Strohl W. R. 1996; Cloning, sequencing, and analysis of aklaviketone reductase from Streptomyces sp. strain C5. J Bacteriol 178:3384–3388
    [Google Scholar]
  11. Draeger G., Park S.-H., Floss H. G. 1999; Mechanism of the 2-deoxygenation step in the biosynthesis of the deoxyhexose moieties of the antibiotics granaticin and oleandomycin. J Am Chem Soc 121:2611–2612 [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. Gaisser S., Böhm G. A., Cortés J., Leadlay P. F. 1997; Analysis of seven genes from the eryAIeryK region of the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea. Mol Gen Genet 256:239–251 [CrossRef]
    [Google Scholar]
  15. Gaisser S., Böhm G. A., Doumith M., Raynal M.-C., Dhillon N., Cortés J., Leadlay P. F. 1998; Analysis of eryBI, eryBIII and eryBVII from the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea. Mol Gen Genet 258:78–88 [CrossRef]
    [Google Scholar]
  16. 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]
  17. 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]
  18. Gourmelen A., Blondelet-Rouault M.-H., Pernodet J.-L. 1998; Characterization of a glycosyl transferase inactivating macrolides, encoded by gimA from Streptomyces ambofaciens. Antimicrob Agents Chemother 42:2612–2619
    [Google Scholar]
  19. Haydock S. F., Dowson J. A., Dhillon N., Roberts G. A., Cortés J., Leadlay P. F. 1991; Cloning and sequence analysis of genes involved in erythromycin biosynthesis in Saccharopolyspora erythraea, sequence similarities between EryG and a family of S-adenosylmethionine-dependent methyltransferases. Mol Gen Genet 230:120–128 [CrossRef]
    [Google Scholar]
  20. Hernandez C., Olano C., Méndez C., Salas J. A. 1993; Characterization of a Streptomyces antibioticus gene cluster encoding a glycosyltransferase involved in oleandomycin inactivation. Gene 134:139–140 [CrossRef]
    [Google Scholar]
  21. Huang S.-L., Hassell T. C., Yeh W.-K. 1993; Purification and properties of NADPH-dependent tylosin reductase from Streptomyces fradiae. J Biol Chem 268:18987–18993
    [Google Scholar]
  22. Ichinose K., Bedford D. J., Tornus D., Bechtold A., Bibb M. J., Revill W. P., Floss H. G., Hopwood D. A. 1998; The granaticin biosynthetic gene cluster of Streptomyces violaceoruber Tü22: sequence analysis and expression in a heterologous host. Chem Biol 5:647–659 [CrossRef]
    [Google Scholar]
  23. Janssen G. R., Bibb M. J. 1993; Derivatives of pUC18 that have BglII 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]
  24. Jenkins G., Cundliffe E. 1991; Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics. Gene 108:55–62 [CrossRef]
    [Google Scholar]
  25. Kagan R. M., Clarke S. 1994; Widespread occurrence of three sequence motifs in diverse S-adenosylmethionine-dependent methyltransferases suggests a common structure for these enzymes. Arch Biochem Biophys 310:417–427 [CrossRef]
    [Google Scholar]
  26. Kim K.-S., Farrand S. K. 1996; Ti plasmid-encoded genes responsible for catabolism of the crown gall opine mannopine by Agrobacterium tumefaciens are homologs of the T-region genes responsible for synthesis of this opine by the plant tumor. J Bacteriol 178:3275–3284
    [Google Scholar]
  27. Macpherson D. F., Manning P. A., Morona R. 1994; Characterization of the dTDP-rhamnose biosynthetic genes encoded in the rfb locus of Shigella flexneri. Mol Microbiol 11:281–292 [CrossRef]
    [Google Scholar]
  28. 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]
  29. Olano C., Rodriguez A. M., Michel J.-M., Méndez C., Raynal M.-C., Salas J. A. 1998; Analysis of a Streptomyces antibioticus chromosomal region involved in oleandomycin biosynthesis, which encodes two glycosyltransferases responsible for glycosylation of the macrolactone ring. Mol Gen Genet 259:299–308 [CrossRef]
    [Google Scholar]
  30. Ōmura S., Sadakane N., Matsubara H. 1982a; Bioconversion and biosynthesis of 16-membered macrolide antibiotics. XXII. Biosynthesis of tylosin after protylonolide formation. Chem Pharm Bull 30:223–229 [CrossRef]
    [Google Scholar]
  31. Ōmura S., Tanaka H., Tsukui M. 1982b; Biosynthesis of tylosin: oxidations of 5-O-mycaminosylprotylonolide at C-20 and C-23 with a cell-free extract from Streptomyces fradiae. Biochem Biophys Res Commun 107:554–560 [CrossRef]
    [Google Scholar]
  32. Pissowotzki K., Mansouri K., Piepersberg W. 1991; Genetics of streptomycin production in Streptomyces griseus: molecular structure and putative function of genes strELMB2N. Mol Gen Genet 231:113–123 [CrossRef]
    [Google Scholar]
  33. Quirós L. M., Aguirrezabalaga I., Olano C., Méndez C., Salas J. A. 1998; Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus. Mol Microbiol 28:1177–1185 [CrossRef]
    [Google Scholar]
  34. Reiser J., Muheim A., Hardegger M., Frank G., Fiechter A. 1994; Aryl-alcohol dehydrogenase from the white rot fungus Phanerochaete chrysosporium. J Biol Chem 269:28152–28159
    [Google Scholar]
  35. Salah-Bey K., Doumith M., Michel J.-M., Haydock S., Cortés J., Leadlay P. F., Raynal M.-C. 1998; Targeted gene inactivation for the elucidation of deoxysugar biosynthesis in the erythromycin producer Saccharopolyspora erythraea. Mol Gen Genet 257:542–553 [CrossRef]
    [Google Scholar]
  36. 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]
  37. Scotti C., Hutchinson C. R. 1996; Enhanced production by manipulation of the Streptomyces peucetius dnrH and dnmT genes involved in doxorubicin (adriamycin) biosynthesis. J Bacteriol 178:7316–7321
    [Google Scholar]
  38. Summers R. G., Donadio S., Staver M. J., Wendt-Pienkowski E., Hutchinson C. R., Katz L. 1997; Sequencing and mutagenesis of genes from the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea that are involved in l-mycarose and d-desosamine production. Microbiology 143:3251–3262 [CrossRef]
    [Google Scholar]
  39. Thorson J. S., Lo S. F., Ploux O., He X., Liu H. W. 1994; Studies of the biosynthesis of 3,6-dideoxyhexoses: molecular cloning and characterization of the asc (ascarylose) region from Yersinia pseudotuberculosis serogroup VA. J Bacteriol 176:5483–5493
    [Google Scholar]
  40. van Wageningen A. M. A., Kirkpatrick P. N., Williams D. H., Harris B. R., Kershaw J. K., Lennard N. J., Jones M., Jones S. J. M., Solenberg P. J. 1998; Sequencing and analysis of genes involved in the biosynthesis of a vancomycin group antibiotic. Chem Biol 5:155–162 [CrossRef]
    [Google Scholar]
  41. Westrich L., Domann S., Faust B., Bedford D., Hopwood D. A., Bechthold A. 1999; Cloning and characterization of a gene cluster from Streptomyces cyanogenus S136 probably involved in landomycin biosynthesis. FEMS Microbiol Lett 170:381–387 [CrossRef]
    [Google Scholar]
  42. 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]
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