Elucidation of the function of two glycosyltransferase genes (lanGT1 and lanGT4) involved in landomycin biosynthesis and generation of new oligosaccharide antibiotics

Axel Trefzer, Carsten Fischer, Sigrid Stockert, Lucy Westrich, Eva Künzel, Ulrich Girreser, Jürgen Rohr, Andreas Bechthold

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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 Tü2717 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 MunI and EcoRI 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.

Original languageEnglish
Pages (from-to)1239-1252
Number of pages14
JournalChemistry and Biology
Issue number12
StatePublished - 2001

Bibliographical note

Funding Information:
We would like to thank Drs. William Cotham, Michael Walla (University of South Carolina, Department of Biochemistry and Chemistry) and Mr. Uwe Rix (Medical University of South Carolina) for the MS data. The work was supported by a Grant of the European Union (QLK3-CT-1999-00095) to A.B. and by grants of the South Carolina Department of Higher Education (2000–2001), in part by MUSC Institutional Research Funds of 1999-00, and the US Department of Defense to J.R.


  • Combinatorial biosynthesis
  • Glycosyltransferase
  • Landomycin
  • Urdamycin
  • Vector system

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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