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Two polyene amides produced by genetically modified Streptomyces diastaticus var. 108
Elena M Seco1, Trinidad Cuesta, Serge Fotso
1Centro Nacional de Biotecnología, Campus de la UAM, 28049 Cantoblanco, Madrid, Spain.
Chemistry & Biology
|May 25, 2005
Summary
Genetic modification of Streptomyces diastaticus var. 108 produced novel polyene macrolide amides. These new compounds exhibit enhanced biological activity and reduced toxicity compared to parent antibiotics.
Area of Science:
- Microbiology
- Molecular Biology
- Medicinal Chemistry
Background:
- Streptomyces diastaticus var. 108 produces polyene macrolide antibiotics rimocidin and CE-108.
- The biosynthetic gene cluster for these antibiotics was partially characterized.
Purpose of the Study:
- To genetically modify Streptomyces diastaticus var. 108 to produce novel macrolide derivatives.
- To characterize the chemical and biological properties of these novel compounds.
Main Methods:
- Genetic modification of the producer strain using SCP2*-derived vectors containing the ermE gene.
- Detection and chemical characterization of novel macrolides in fermentation broth.
- Evaluation of biological activity and in vitro toxicity assays.
Main Results:
- Two previously uncharacterized macrolides were detected in the genetically modified strain.
- These novel macrolides were identified as amides of the parental polyene carboxylic acids.
- The modified macrolides demonstrated improved biological properties and reduced toxicity compared to parent compounds.
Conclusions:
- Genetic engineering of Streptomyces diastaticus var. 108 can yield novel polyene macrolide amides.
- These derivatives represent potential pharmaceuticals with superior therapeutic profiles.