Elucidation of the function of two glycosyltransferase genes (lanGT1 and lanGT4) involved in landomycin biosynthesis and generation of new oligosaccharide antibiotics
| Autor: | Jürgen Rohr, Carsten Fischer, Axel Trefzer, Ulrich Girreser, Sigrid Stockert, Lucy Westrich, Eva Künzel, Andreas Bechthold |
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| Rok vydání: | 2001 |
| Předmět: |
Magnetic Resonance Spectroscopy
Combinatorial biosynthesis Vector system Genetic Vectors Mutant Clinical Biochemistry Landomycin Biology Streptomyces Biochemistry chemistry.chemical_compound Polyketide Glycosyltransferase Gene cluster Drug Discovery Urdamycin Molecular Biology DNA Primers Pharmacology Glycosyltransferase Gene Glycosyltransferases Sequence Analysis DNA General Medicine Streptomyces fradiae biology.organism_classification Anti-Bacterial Agents Aminoglycosides chemistry Genes Bacterial Multigene Family Mutation biology.protein Molecular Medicine |
| Zdroj: | Chemistry & Biology. 8(12):1239-1252 |
| ISSN: | 1074-5521 |
| DOI: | 10.1016/s1074-5521(01)00091-6 |
| Popis: | Background: The genetic engineering of antibiotic-producing Streptomyces strains is an approach that became a successful methodology in developing new natural polyketide derivatives. Glycosyltransferases are important biosynthetic enzymes that link sugar moieties to aglycones, which often derive from polyketides. Biological activity is frequently generated along with this process. Here we report the use of glycosyltransferase genes isolated from the landomycin biosynthetic gene cluster to create hybrid landomycin/urdamycin oligosaccharide antibiotics. Results: Production of several novel urdamycin derivatives by a mutant of Streptomyces fradiae Tu2717 has been achieved in a combinatorial biosynthetic approach using glycosyltransferase genes from the landomycin producer Streptomyces cyanogenus S136. For the generation of gene cassettes useful for combinatorial biosynthesis experiments new vectors named pMUNI, pMUNII and pMUNIII were constructed. These vectors facilitate the construction of gene combinations taking advantage of the compatible Mun I and Eco RI restriction sites. Conclusions: The high-yielding production of novel oligosaccharide antibiotics using glycosyltransferase gene cassettes generated in a very convenient way proves that glycosyltransferases can be flexible towards the alcohol substrate. In addition, our results indicate that LanGT1 from S. cyanogenus S136 is a D-olivosyltransferase, whereas LanGT4 is a L-rhodinosyltransferase. |
| Databáze: | OpenAIRE |
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