AB023, novel polyene antibiotics. I. Taxonomy of the producing organism, fermentation and antifungal activity.

AB023 is a complex of polyene antibiotics produced by an actinomycete, SD581, which was isolated from a Kenyan soil sample. The two main components, pentaene antibiotics AB023a and AB023b, have antifungal activity against some phytopathogenic fungi, particularly against Botrytis cinerea (MIC of 5 micrograms/ml).

Genetic and biochemical characterization of a ribosomal mutant of Bacillus subtilis resistant to sporangiomycin.

The antibiotic sporangiomycin affects the growth of Bacillus subtilis by inhibiting protein synthesis. Mutants of B. subtilis resistant to sporangiomycin have been isolated. One of these, PB 1690, has been further studied. The analysis of subcellular fractions from the mutant has shown that the biochemical effect of the mutation is an alteration of a site on the 50S ribosomal subunit responsible for the binding of the antibiotic: the mutant ribosomes do not bind sporangiomycin and are capable of carrying out phenylalanine polymerization in the presence of sporangiomycin. The resistance mutation maps on the chromosomal region where the ribosomal markers map. The mutant strain is also resistant to the action of the chemically related antibiotic thiostrepton. Treatment of B. subtilis ribosomes with LiCl results in the detachment of a group of proteins including the one responsible for sporangiomycin resistance. Active ribosomes can be reconstructed by mixing "split proteins" and "core particles" of either parental or mutant origin. The fate of the mutant protein can now be followed by assaying reconstructed ribosomes for capacity to bind sporangiomycin and for resistance to the action of the antibiotic in the reactions for phenylalanine polymerization.

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

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.