Sclerothricin is a new strongly basic antibiotic obtained from the culture filtrate of Streptomyces sclerogranulatus SHIMAZU et YONEHARA nov. sp. The antibiotic is active against gram-positive and gram-negative bacteria and some fungi. Sclerothricin (C16H30O8N6) seems to belong to the streptothricin group. It has two N-methyl, a free carboxyl and two N-terminal groups. No carbamoyl group is present.
Six strains of Streptomyces, all producing sclerothricin and forming sclerotic granules on their vegetative mycelium, have been isolated from soil samples of Japan. A comparison of the characteristics of these strains with related Streptomyces indicates that these should belong to a new species, named by us as S. sclerogranulatus SHIMAZU et YONEHARA sp. nov. with No.7672-MC4 as the type strain.
The new antibiotic, moenomycin, isolated from Streptomyces bambergiensis is a mixture of several, chemically very similar components, which are particularly characterized by their phosphorus content. The moenomycin complex can be separated into components A, B1, B2 and C by means of column chromatography on silica gel with n-propanol - 2N ammonia as eluant. The use of other chromatographic procedures, e. g. chromatography on anion exchange resins, results in a further separation of fraction B1 into components D, E and F ; similarly fraction B2 can be separated into components G and H. Isolation and properties of moenomycins D, E, F, G and H are described.
Antibacterial activity of 16 chloramphenicol derivatives and their induction ability for chloramphenicol resistance were examined. Three chloramphenicol derivatives ; CM 16 (DL-α-dichloroacetamido-β-bromo-p-nitropropiophenone), CM 17 (DL-α-dichloroacetamido-α-methylene-p-nitropropiophenone) and CM 18 (DL-α-acetamido-α-methylene-p-nitro-propiophenone) were found to be highly active against S-1477 but their inducible activity for chloramphenicol resistance was rather low. CM 26 (chloramphenicol monophosphate) and CM 29 (D-threo-2, 2-diethyl-5-dichloroacetamido-6-(p-nitrophenyl)-1, 3-dioxane) has no antibacterial activity and CM 15 (DL-threo-2-dichloromethyl-4-p-nitrophenyl-hydroxymethyl-Δ2-oxazoline) has very low activity against S-1477, but they have low inducible activity for chloramphenicol resistance in spite of no activity of other derivatives.
Mitocrominis an antibiotic composed of an equilibrium mixture of two components A and B. The antibiotic is related to daunomycin which also accompanies mitocromin in the culture broth. Mitocromin has antitumor activity as shown in test systems: WALKER 256 carcinosarcoma in rats and Leukemia P-388 in mice.
The localization in ribosomes of sensitivity to kanamycin was investigated and compared with that to streptomycin, using ribosomes from a mutant of Escherichia coli resistant to both these antibiotics. It was demonstrated that the sensitivity to both antibiotics was located in the 30S subunit. The 30S subunit was fractionated into a 23S core and split proteins 30, and the 23S core was split further into core proteins 30 and 16S ribosomal RNA. It was found that the sensitivity to kanamycin as well as to streptomycin resided in proteins of the 23S core. To identify the responsible component, 30S ribosomal proteins from the parent strain and from a kanamycin-resistant mutant were labelled differently, and co-chromatographed through carboxymethylcellulose column. Only one component (P10) was observed to appear inconsistently in the elution profile, and it was therefore assumed to be the component that determined the sensitivity to kanamycin. This assumption was confirmed by examining the inhibition by kanamycin in poly U-directed incorporation of phenylalanine with 30S subunits reconstituted in different combinations between P10 and the other components from the two origins. This component and the component controlling sensitivity to streptomycin were identical. It was observed that the reconstituted ribosomes containing P10 from either resistant mutant were resistant to both antibiotics, and P10 protein in both mutants was altered.
Effect of bleomycin and H2O2 on DNA was investigated. Tm of salmon sperm DNA decreased from 76°C to 64°C and that of Escherichia coli DNA from 81°C to 65.5°C in the presence of 100μM of H2O2 and 4μg/ml of bleomycin. The change of Tm was more marked when the concentration of H2O2 or bleomycin was increased. The single strand scission of DNA was shown when the DNA was incubated at 37°C with 100μM of H2O2 and 40μg/ml of bleomycin. It proceeded as the time of incubation was prolonged. The reaction of H2O2 at 100μM on DNA was apparent only in the presence of bleomycin.
Kujimycins A and B obtained from the fermentation broth of Streptomyces spinichromogenes var. kujimyceticus have already been reported as neutral macrolides exhibiting activities against Gram-positive bacteria1). Recently, in the course of structural investigation, kujimycin B has been found to be identical with an authentic specimen of lankamycin. The structure of kujimycin A has been elucidated by some chemical degradation studies as lankamycin deacetylated at C-4 of arcanose.