ABSTRACT
Metyrapone, a potent cytochrome P-450 inhibitor, added at 9 mM to a submerged culture of Streptomyces cinnamonensis caused partial inhibition of total monensin biosynthesis and coproduction of new metabolites, 26-deoxymonensins A and B. The latter was isolated as its 25-O-methyl derivative. Metyrapone was simultaneously reduced to metyrapol. All of these compounds were identified by nuclear magnetic resonance spectroscopy and mass spectrometry.
Subject(s)
Anti-Bacterial Agents/biosynthesis , Pyridines/pharmacology , Streptomyces/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Magnetic Resonance Spectroscopy , Mass Spectrometry , Metyrapone/analogs & derivatives , Metyrapone/metabolism , Monensin/analogs & derivatives , Monensin/biosynthesis , Monensin/chemistry , Monensin/isolation & purification , Pyridines/metabolism , Streptomyces/drug effectsABSTRACT
Analytical and preparative high-performance liquid chromatography of 3 phenazines and furonaphthoquinone derivative on reversed-phase column are described. The mobile phase was methanol and water. The injected amount of the mixture was about 30 mg for a preparative chromatographic run requiring 80 min. Substances were detected directly in the column effluent by UV detection.
Subject(s)
Chromatography, High Pressure Liquid , Phenazines/isolation & purification , Streptomyces/analysis , Furans/isolation & purification , Naphthoquinones/isolation & purificationABSTRACT
The interaction of granaticin B, a quinone antibiotic produced by Streptomyces granaticolor, with some biologically important bivalent metal ions, DNA and ATP was demonstrated spectrophotometrically. The activity of isolated RNA polymerase was higher when the DNA of phage SP 50 served as template than with DNA isolated from Bacillus subtilis. Granaticin B inhibited in vitro RNA synthesis, similarly to certain other antibiotics (the inhibition was three times lower than that caused by actinomycin D or streptolydigin and slightly higher than that by epsilon-pyrromycinone). The inhibitory effect was higher when the Mg2+ concentration in the reaction mixture was decreased. The inhibition was then proportional to the concentration of the DNA template. DNA-dependent RNA synthesis is thus inhibited in vitro by granaticin B but this does not appear to be the only site of action of this antibiotic in vivo.
