Improved Mutasynthetic Approaches for the Production of Modified Aminocoumarin Antibiotics
| Autor: | Bernd Kammerer, Christine Anderle, Ludger A. Wessjohann, Bertolt Gust, Shu-Ming Li, Susanne Hennig, Lutz Heide |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Aminocoumarins
Spectrometry Mass Electrospray Ionization Staphylococcus aureus Stereochemistry medicine.drug_class Antibiotics Clinical Biochemistry Microbial Sensitivity Tests Biochemistry Substrate Specificity chemistry.chemical_compound Coumarins Amide Drug Discovery medicine Moiety Molecular Biology Chromatography High Pressure Liquid Novobiocin DNA Primers Chembio Pharmacology Clorobiocin Base Sequence Chemistry Microbio General Medicine Anti-Bacterial Agents Pseudomonas aeruginosa Substrate specificity Molecular Medicine medicine.drug |
| Zdroj: | Chemistry & Biology. 14(8):955-967 |
| ISSN: | 1074-5521 |
| DOI: | 10.1016/j.chembiol.2007.07.014 |
| Popis: | Summary This study reports improved mutasynthetic approaches for the production of aminocoumarin antibiotics. Previously, the mutasynthetic production of aminocoumarins with differently substituted benzoyl moieties was limited by the substrate specificity of the amide synthetase CloL. We expressed two amide synthetases with different substrate specificity, CouL and SimL, in appropriately engineered producer strains. After feeding of precursor analogs that were not accepted by CloL, but by SimL or CouL, a range of aminocoumarins, unattainable in our previous experiments, was produced and isolated in preparative amounts. Further, we developed a two-stage mutasynthesis procedure for the production of hybrid antibiotics that showed the substitution pattern of novobiocin in the aminocoumarin moiety and that of clorobiocin in the deoxysugar moiety. The substitution pattern of the benzoyl moiety was determined by external addition of an appropriate precursor. Twenty-five aminocoumarin compounds were prepared by these methods, and their structures were elucidated with mass and 1 H-NMR spectroscopy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|