Lipiarmycin, a new antibiotic from Actinoplanes III. Mechanism of action

Abstract

In vivo, at low concentrations (less than or equal to 1 mug/ml), the antibiotic lipiarmycin specifically inhibits RNA synthesis in Bacillus subtilis. At a much higher concentration (100 mug/ml), syntheses of other macromolecules such as DNA and protein also appear to be suppressed. In vitro, the antibiotic caused 50% inhibition of DNA-dependent RNA-polymerase from B. subtilis at a concentration of 0.6 mug/ml and of that E. coli at 5 approximately 8 mug/ml. The activity of Escherichia coli DNA-polymerase I is inhibited 50% at 55 approximately 65 mug/ml. Lipiarmycin prevent ribonucleoside triphosphate polymerization only if added prior to the association between RNA-polymerase and DNA, and does not affect the elongation rate of RNA chains at concentrations up to 100 mug/ml. At that concentration, however, the antibiotic immediately blocks the polymerization of deoxyribonucleotide triphosphates catalyzed by DNA-polymerase I.