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

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 land-omycin/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 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 LanGTI from S. cyanogenus S136 is a (D)-olivosyltransferase, whereas LanGT4 is a (L)-rhodinosyltransferase. (C) 2001 Elsevier Science Ltd. All rights reserved.