ABSTRACT
Streptomyces sp. KM1-30 was isolated from soil as a producer of antimutagens by screening with a modified Ames test. The chemical structure of the antimutagenic metabolite was identified as streptovaricin C, which is known to inhibit DNA dependent RNA polymerase from E. coli and RNA dependent DNA polymerase from RNA tumor viruses, by MS and 1H-, 13C-NMR analyses. Addition of streptovaricin C to the cultures of UV treated Salmonella typhimurium TA100 or Trp-P-2-treated S. typhimurium TA98 decreased the frequency of mutation without a decrease in viable cell counts. The effect of streptovaricin C to the mutation induced by UV and Trp-P-2 was not desmutagenic, but antimutagenic.
Subject(s)
Antimutagenic Agents/isolation & purification , Streptomyces/chemistry , Streptovaricin/analogs & derivatives , Actinomycetales/drug effects , Actinomycetales/genetics , Antimutagenic Agents/chemistry , Antimutagenic Agents/pharmacology , Molecular Structure , Mutagenicity Tests , Streptovaricin/chemistry , Streptovaricin/isolation & purification , Streptovaricin/pharmacologyABSTRACT
Morphological, cultural and physiological-biochemical properties of Streptomyces sp. strain 1000 and its antibiotic production were investigated. Antibiotics 1011 (identical with the streptovaricin complex) and 1012 (with antibacterial action) were isolated from the cultural broth of this strain. The overproducing natural variant 1011 was isolated from the population of a strain producing antibiotic 1011 at a concentration of 1000 mg/L (activity of the parent strain represents 41 mg/L only). Comparative taxonomical characteristic of Streptomyces sp. strain 1000 with strains from S. spectabilis showed that the strain 1000 differed in some properties and antibiotic production being considered as a new variant of S. spectabilis. The strain shows an expressed antibiotic activity against G+ as well as G- bacterial and yeasts.
Subject(s)
Streptomyces/metabolism , Streptovaricin/biosynthesis , Hydrogen-Ion Concentration , Species Specificity , Streptomyces/classification , Streptovaricin/isolation & purificationABSTRACT
Damavaricin C, a degradative derivative of streptovaricin C, has reduced antibiotic activity relative to streptovaricin C. It has, however, a new phenolic hydroxyl group at the C-19 position of the naphthoquinone ring on which various groups can be substituted through an ether linkage. A series of 19-O-substituted derivatives of damavaricin C has been synthesized. The preparation of these derivatives, their in vitro antibacterial activities, in vitro inhibition of E. coli RNA polymerase, and lethal activity on the membrane mutants of E. coli are reported. It is believed that the original biological activity of damavaricin C is retained and that introduction of the functional groups at the C-19 position has increased the membrane diffusibility of the molecule.
Subject(s)
Streptovaricin/chemical synthesis , Bacteria/drug effects , Chemical Phenomena , Chemistry , DNA-Directed RNA Polymerases/antagonists & inhibitors , Escherichia coli/drug effects , Escherichia coli/enzymology , Hydrolysis , Oxygen , Streptovaricin/isolation & purification , Streptovaricin/pharmacologyABSTRACT
Chromatographic fractionation of streptovaricin complex yields two stable components enriched (4- to 16-fold) in activity directed against the polycythemic strain of Friend virus; both components apparently contain no streptovaricins. When compared with their unfractionated parent streptovaricin complex, eight individual intact streptovaricins (A through G and J) show at least a 30-fold reduction in antiviral activity. These results further support the conclusion that the diversified biological properties of streptovaricin complex probably reside in different molecular structures.
