1887

Abstract

The glycopeptide teicoplanin is used for the treatment of serious infections caused by Gram-positive pathogens. The gene cluster, devoted to teicoplanin biosynthesis in the actinomycete , was isolated and characterized. From sequence analysis, the cluster spans approximately 73 kb and includes 39 ORFs participating in teicoplanin biosynthesis, regulation, resistance and export. Of these, 34 ORFs find a match in at least one of the five glycopeptide gene clusters previously characterized. Putative roles could be assigned for most of the genes. The two glycosyltransferases responsible for attaching amino sugars to amino acids 4 and 6 of the teicoplanin aglycon were overexpressed in and characterized. They both recognize -acetylglucosamine as the substrate. tGtfA can add a sugar residue in the presence or absence of -acetylglucosamine at amino acid 4, while tGtfB can only glycosylate the teicoplanin aglycon.

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2004-01-01
2024-11-13
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References

  1. Barth S., Huhn M., Matthey B., Klimka A., Galinski E. A., Engert A. 2000; Compatible-solute-supported periplasmic expression of functional recombinant proteins under stress conditions. Appl Environ Microbiol 66:1572–1579 [CrossRef]
    [Google Scholar]
  2. Bentley S. D., Chater K. F., Cerdeno-Tarraga A. M. & 40 other authors; 2002; Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). . Nature 417:141–147 [CrossRef]
    [Google Scholar]
  3. Bischoff D., Pelzer S., Höltzel A., Nicholson G., Stockert S., Wohlleben W., Jung G., Sußmuth R. 2001a; The biosynthesis of vancomycin-type glycopeptide antibiotics – new insights into the cyclization steps. Angew Chem Int Ed 40:1693–1696 [CrossRef]
    [Google Scholar]
  4. Bischoff D., Pelzer S., Bister B., Nicholson G. J., Stockert S., Schirle M., Wohlleben W., Jung G., Sußmuth R. D. 2001b; The biosynthesis of vancomycin-type glycopeptide antibiotics – the order of cyclization steps. Angew Chem Int Ed 40:4688–4691 [CrossRef]
    [Google Scholar]
  5. Chen H., Walsh C. T. 2001; Coumarin formation in novobiocin biosynthesis: β-hydroxylation of the aminoacyl enzyme tyrosyl-S-NovH by a cytochrome P450 NovI. Chem Biol 74:1–12
    [Google Scholar]
  6. Chen H., Tseng C. C., Hubbard B. K., Walsh C. T. 2001; Glycopeptide antibiotic biosynthesis: enzymatic assembly of the dedicated amino acid monomer (S)-3,5-dihydroxyphenylglycine. Proc Natl Acad Sci U S A 98:14901–14906 [CrossRef]
    [Google Scholar]
  7. Chiu H. T., Hubbard B. K., Shah A. N., Eide J., Fredenburg R. A., Walsh C. T., Khosla C. 2001; Molecular cloning and sequence analysis of the complestatin biosynthetic gene cluster. Proc Natl Acad Sci U S A 98:8548–8553 [CrossRef]
    [Google Scholar]
  8. Evers S., Quintiliani R. Jr, Courvalin P. 1996; Genetics of glycopeptide resistance in enterococci. Microb Drug Resist 2:219–223 [CrossRef]
    [Google Scholar]
  9. Heathcote M. L., Staunton J., Leadlay P. F. 2001; Role of type II thioesterases: evidence for removal of short acyl chains produced by aberrant decarboxylation of chain extender units. Chem Biol 8:207–220 [CrossRef]
    [Google Scholar]
  10. Hodgson D. A. 2000; Primary metabolism and its control in streptomycetes: a most unusual group of bacteria. Adv Microb Physiol 42:47–238
    [Google Scholar]
  11. Hojati Z., Milne C., Harvey B. & 9 other authors; 2002; Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor. Chem Biol 9:1175–1187 [CrossRef]
    [Google Scholar]
  12. Hubbard B. K., Walsh C. T. 2003; Vancomycin assembly: nature's way. Angew Chem Int Ed 42:731–765
    [Google Scholar]
  13. Hubbard B. K., Thomas M. G., Walsh C. T. 2000; Biosynthesis of l-p-hydroxyphenylglycine, a non-proteinogenic amino acid constituent of peptide antibiotics. Chem Biol 7:931–942 [CrossRef]
    [Google Scholar]
  14. Li T. L., Choroba O. W., Charles E. H., Sandercock A. M., Williams D. H., Spencer J. B. 2001; Characterisation of a hydroxymandelate oxidase involved in the biosynthesis of two unusual amino acids occurring in the vancomycin group of antibiotics. Chem Commun 20011752–1753
    [Google Scholar]
  15. Losey H. C., Peczuh M. W., Chen Z., Eggert U. S., Dong S. D., Pelczer I., Kahne D., Walsh C. T. 2001; Tandem action of glycosyltransferases in the maturation of vancomycin and teicoplanin aglycones: novel glycopeptides. Biochemistry 40:4745–4755 [CrossRef]
    [Google Scholar]
  16. Losey H. C., Jiang J., Biggins J. B., Oberthür M., Ye X.-Y., Dong S. D., Kahne D., Thorson J. S., Walsh C. T. 2002; Incorporation of glucose analogs by GtfE and GtfD from the vancomycin biosynthetic pathway to generate variant glycopeptides. Chem Biol 9:1305–1314 [CrossRef]
    [Google Scholar]
  17. Malabarba A., Ciabatti R. 2001; Glycopeptide derivatives. Curr Med Chem 8:1759–1773 [CrossRef]
    [Google Scholar]
  18. Malabarba A., Strazzolini P., Depaoli A., Landi M., Berti M., Cavalleri B. 1984; Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov. sp. VI. Chemical degradation: physico-chemical and biological properties of acid hydrolysis products. J Antibiot 37:988–999 [CrossRef]
    [Google Scholar]
  19. Marahiel M. A. 1997; Protein templates for the biosynthesis of peptide antibiotics. Chem Biol 4:561–567 [CrossRef]
    [Google Scholar]
  20. Pelzer S., Süßmuth R., Heckmann D., Recktenwald J., Huber P., Jung G., Wohlleben W. 1999; Identification and analysis of the balhimycin biosynthetic gene cluster and its use for manipulating glycopeptide biosynthesis in Amycolatopsis mediterranei DSM5908. . Antimicrob Agents Chemother 43:1565–1573
    [Google Scholar]
  21. Pfeifer V., Nicholson G. J., Ries J., Recktenwald J., Schefer A. B., Shawky R., Schröder J., Wohlleben W., Pelzer S. 2001; A polyketide synthase in glycopeptide biosynthesis: the biosynthesis of the non-proteinogenic amino acid (S)-3,5-dihydroxyphenylglycine. J Biol Chem 276:38370–38377 [CrossRef]
    [Google Scholar]
  22. Pootoolal J., Thomas M. G., Marshall C. G., Neu J. M., Hubbard B. K., Walsh C. T., Wright G. D. 2002; Assembling the glycopeptide antibiotic scaffold: the biosynthesis of A47934 from Streptomyces toyocaensis NRRL15009. . Proc Natl Acad Sci U S A 99:8962–8967 [CrossRef]
    [Google Scholar]
  23. Puk O., Huber P., Bischoff D., Recktenwald J., Jung G., Süßmuth R. D., Van Pee K.-H., Wohlleben W., Pelzer S. 2002; Glycopeptide biosynthesis in Amycolatopsis mediterranei: function of a halogenase and a haloperoxidase/perhydrolase. Chem Biol 9:225–235 [CrossRef]
    [Google Scholar]
  24. Recktenwald J., Shawky R., Puk O., Pfennig F., Keller U., Wohlleben W., Pelzer S. 2002; Nonribosomal biosynthesis of vancomycin-type antibiotics: a heptapeptide backbone and eight peptide synthetase modules. Microbiology 148:1105–1118
    [Google Scholar]
  25. Schwarzer D., Mootz H. D., Linne U., Marahiel M. 2002; Regeneration of misprimed nonribosomal peptide synthetases by type II thioesterases. Proc Natl Acad Sci U S A 99:14083–14088 [CrossRef]
    [Google Scholar]
  26. Solenberg P. J., Matsushima P., Stack D. R., Wilkie S. C., Thompson R. C., Baltz R. H. 1997; Production of hybrid glycopeptide antibiotics in vitro and in Streptomyces toyocaensis. Chem Biol 4:195–202 [CrossRef]
    [Google Scholar]
  27. Sosio M., Bianchi A., Bossi E., Donadio S. 2000; Teicoplanin biosynthesis genes in Actinoplanes teichomyceticus. Antonie Van Leeuwenhoek 78:379–384 [CrossRef]
    [Google Scholar]
  28. Sosio M., Stinchi S., Beltrametti B., Lazzarini A., Donadio S. 2003; The gene cluster for the biosynthesis of the glycopeptide antibiotic A40926 by Nonomuraea species. Chem Biol 10:541–549 [CrossRef]
    [Google Scholar]
  29. van Wageningen A. M., Kirkpatrick P. N., Williams D. H., Harris B. R., Kershaw J. K., Lennard N. J., Jones M., Jones S. J., 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]
  30. Zazopoulos E., Farnet C. M., Staffa A. 2002 Gene cluster for ramoplanin biosynthesis. Patent WO 0231155-A 1 18-APR-2002 Ecopia Biosciences Inc. (CA); Accession AX417445
    [Google Scholar]
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