RESUMEN
3-Acetyl analogues of thiolactomycin, a thiotetronic acid natural product, were synthesized and profiled against livestock pathogens. Some analogues showed improved activity over thiolactomycin against Staphylococcus aureus and comparable activity against Pasteurella multocida. Several semisynthetically modified analogues of thiolactomycin showed no improvement in activity over thiolactomycin.
Asunto(s)
Antibacterianos/síntesis química , Tiofenos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Tiofenos/química , Tiofenos/farmacologíaRESUMEN
Cyclopropane carboxylic acid was fed to Saccharopolyspora erythraea NRRL 18643 (6-deoxyerythromycin producer), resulting in the production of 6-deoxy-13-cyclopropyl-erythromycin B. These studies provide further evidence that deoxyerythronolide B synthase has a relaxed specificity for the starter unit.
Asunto(s)
Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacología , Eritromicina/análogos & derivados , Macrólidos , Saccharopolyspora/metabolismo , Ciclopropanos/metabolismo , Eritromicina/química , Eritromicina/metabolismo , Eritromicina/farmacología , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Saccharopolyspora/genéticaRESUMEN
In a previous report, a plasmid, pIG1, which contained the loading domain from the Streptomyces avermitilis polyketide synthase (PKS), promoters from Streptomyces coelicolor and the DEBS1-TE truncated PKS from Saccharopolyspora erythraea, was integrated into the S. erythraea chromosome, effectively replacing the natural erythromycin loading domain with the avermectin loading domain. In this paper, we report the feeding of short-chained fatty acids to this recombinant strain, and its parent, NRRL 2338. Both strains incorporated exogenously supplied fatty acids to produce novel, biologically active, C-13 substituted erythromycins.