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Glycosyltransferases and Other Tailoring Enzymes as Tools for the Generation of Novel Compounds

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Biocombinatorial Approaches for Drug Finding

7.7 Conclusion

Glycosyltransferases are a very important class of enzymes which can be found in biosynthetic gene clusters of a variety of natural compounds. Some of these GTs show a remarkable flexibility towards the donor and the acceptor molecules making them most valuable for combinatorial biosynthesis. Future work is expected to focus on learning more about sugar biosynthesis, sugar modification and sugar attachment to support in vivo engineering of novel natural products.

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References

  • Blanco G, Patallo EP, Braña AF, Trefzer A, Bechthold A, Rohr J, Méndez C, Salas JA (2001) Identification of a sugar flexible glycosyltransferase from Streptomyces olivaceus, the producer of the antitumor polyketide elloramycin. Chem Biol 8:253–261

    Article  PubMed  CAS  Google Scholar 

  • Crow RT, Rosenbaum B, Smith R, 3rd, Guo Y, Ramos KS, Sulikowski GA (1999) Landomycin A inhibits DNA synthesis and G1/S cell cycle progression. Bioorg Med Chem Lett 9:1663–1666

    Article  PubMed  CAS  Google Scholar 

  • Dürr C, Hoffmeister D, Wohlert SE, Ichinose K, Weber M, von Mulert U, Thorson JS, Bechthold A (2004) The glycosyltransferase UrdGT2 establishes both C-and O-glycosidic bonds. Angewandte (submitted)

    Google Scholar 

  • Faust B, Hoffmeister D, Weitnauer G, Westrich L, Haag S, Schneider P, Decker H, Künzel E, Rohr J, Bechthold A (2000) Two new tailoring enzymes, a glycosyltransferase and an oxygenase, involved in biosynthesis of the angucycline antibiotic urdamycin A in Streptomyces fradiae. Microbiology 146:147–154

    PubMed  CAS  Google Scholar 

  • Hoffmeister D, Dräger G, Ichinose K, Rohr J, Bechthold A (2003) The C-glycosyltransferase UrdGT2 is unselective towards D-and L-configurated nucleotide-bound rhodinose. J Am Chem Soc 125:4678–4679

    Article  PubMed  CAS  Google Scholar 

  • Hoffmeister D, Ichinose K, Bechthold A (2001) Two sequence elements of glycosyltransferases involved in urdamycin biosynthesis are responsible for substrate specificity and enzymatic activity. Chem Biol 8:557–567

    Article  PubMed  CAS  Google Scholar 

  • Hoffmeister D, Ichinose K, Domann S, Faust B, Trefzer A, Drager G, Kirschning A, Fischer C, Künzel E, Bearden DW, Rohr J, Bechthold A (2000) The NDP-sugar co-substrate concentration and the enzyme expression level influence the substrate specificity of glycosyltransferases: Cloning and characterization of deoxysugar biosynthetic genes of the urdamycin biosynthetic gene cluster. Chem Biol 7:821–831

    Article  PubMed  CAS  Google Scholar 

  • Hoffmeister D, Weber M, Dräger G, Ichinose K, Dürr C, Bechthold A (2004) Overexpression of the landomycin glycosyltransferase gene lanGT4 in Streptomyces fradiae Tü2717 resulted in the conversion of the urdamycin trisaccharide into an unnatural tetrasaccharide by transfer of an L-rhodinose unit. ChemBioChem 5:1–4

    Article  Google Scholar 

  • Hoffmeister D, Wilkinson B, Foster G, Sidebottom PJ, Ichinose K, Bechthold A (2002) Engineered urdamycin glycosyltransferases are broadened and altered in substrate specificity. Chem Biol 9:287–295

    Article  PubMed  CAS  Google Scholar 

  • Künzel E, Faust B, Oelkers C, Weißbach U, Bearden D, Weitnauer G, Westrich L, Bechthold A, Rohr J (1999) Inactivation of the urdGt2 gene, which encodes a glycosyl transferase responsible for the C-glycosyltransfer of activated D-olivose, leads to the formation of three novel urdamycins I, J and K. J Am Chem Soc 121:11058–11062

    Article  Google Scholar 

  • Luzhetskyy A, Fedoryshyn M, Hoffmeister D, Bechthold A, Fedorenko V (2002) A gene cloning system for Streptomyces cyanogenus SI36. Biovinsky (Ukraine) 29:62–68

    Google Scholar 

  • Mosbacher TG, Bechthold A, Schulz GE (2003) Crystal structure of the avilamycin resistance-conferring methyltransferase AviRa from Streptomyces viridochromo genes. J Mol Biol 329:147–157

    Article  PubMed  CAS  Google Scholar 

  • Pelzer S, Hoffmeister D, Merfort I, Bechthold A (2004) Procaryotic and eucaryotic cells in biotech production. In: Kayser O, Müller RH, Pharmaceutical biotechnology. Wiley VCH (in press)

    Google Scholar 

  • Rodriguez L, Aguirrezabalaga I, Allende N, Braña AF, Méndez C, Salas JA (2002) Engineering deoxysugar biosynthetic pathways from antibioticproducing microorganisms. A tool to produce novel glycosylated bioactive compounds. Chem Biol 9:721–729

    Article  PubMed  CAS  Google Scholar 

  • Treede I, Jacobsen L, Kirpekar F, Vester B, Weitnauer G, Bechthold A, Douthwait S (2003) The avilamycin resistance genes aviRa and aviRb of Streptomyces viridochromogenes Tü57 encode two methyltransferases that target in G2535 and U2479 in domain V of the 23S rRNA. Mol Microbiol 49:309–318

    Article  PubMed  CAS  Google Scholar 

  • Trefzer A, Blanco G, Remsing L, Künzel E, Rix U, Lipata F, Braña AF, Méndez C, Rohr J, Bechthold A, Salas JA (2002 a) Rationally designed glycosylated premithramycins: hybrid aromatic polyketides using genes from three different biosynthetic pathways. J Am Chem Soc 124:6056–6062

    Article  PubMed  CAS  Google Scholar 

  • Trefzer A, Fischer C, Stockert S, Westrich L, Künzel E, Girreser U, Rohr J, Bechthold A (2001) Elucidation of the function of two glycosyltransferase genes (lanGT1 and lanGT4) involved in landomycin biosynthesis and generation of new oligosaccharide antibiotics. Chem Biol 8:1239–1252

    Article  PubMed  CAS  Google Scholar 

  • Trefzer A, Hoffmeister D, Westrich L, Weitnauer G, Stockert S, Künzel E, Rohr J, Fuchser J, Bindseil K, Bechthold A (2000 a) Function of glycosyltransferase genes involved in the biosynthesis of urdamycin A. Chem Biol 7:133–142

    Article  PubMed  CAS  Google Scholar 

  • Trefzer A, Pelzer S, Schimana J, Stockert S, Bihlmaier C, Fiedler HP, Welzel K, Vente A, Bechthold A (2002 b) The biosynthetic gene cluster of simocyclinone, a natural multihybrid antibiotic. Antimicrob Agents Chemother 46:1174–1182

    Article  PubMed  CAS  Google Scholar 

  • von Mulert U, Luzhetskyy A, Hofmann C, Mayer A, Bechthold A (2004) Expression of the landomycin biosynthetic gene cluster in a PKS mutant of S. fradiae is dependent on the coexpression of a putative transcriptional activator gene. FEMS Microbiol Lett 230:91–97

    Article  Google Scholar 

  • Weitnauer G, Gaisser S, Trefzer A, Stockert S, Westrich L, Quiros LM, Méndez C, Salas J, Bechthold A (2001 a) An ATP-binding cassette transporter and two rRNA methyltransferases are involved in resistance to avilamycin in the producer organism Streptomyces viridochromogenes Tü57. Antimicrob Agents Chemother 45:690–695

    Article  PubMed  CAS  Google Scholar 

  • Weitnauer G, Gaisser S, Kellenberger L, Leadlay PF, Bechthold A (2002 a) Analysis of a C-methyltransferase gene iaviG1) involved in avilamycin biosynthesis in Streptomyces viridochromogenes Tü57 and complementation of a Saccharopolyspora erythraea eryBIII mutant by aviG1. Microbiology 148:373–379

    PubMed  CAS  Google Scholar 

  • Weitnauer G, Hauser G, Linder U, Hofmann C, Glaser SJ, Bechthold A (2004) Novel avilamycin derivatives with improved polarity generated by targeted gene disruption. Chem Biol (accepted)

    Google Scholar 

  • Weitnauer G, Mühlenweg A, Trefzer A, Hoffmeister D, Süßmuth R, Jung G, Welzel K, Vente A, Girresser U, Bechthold A (2001b) Biosynthesis of the orthosomycin antibiotic avilamycin A: deductions from the molecular analysis of the avi biosynthetic gene cluster of Streptomyces viridochromogenes Tü57 and production of new antibiotics. Chem Biol 8:569–581

    Article  PubMed  CAS  Google Scholar 

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Bechthold, A. et al. (2005). Glycosyltransferases and Other Tailoring Enzymes as Tools for the Generation of Novel Compounds. In: Wohlleben, W., Spellig, T., Müller-Tiemann, B. (eds) Biocombinatorial Approaches for Drug Finding. Ernst Schering Research Foundation Workshop, vol 51. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-27055-8_7

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