Most cited article - PubMed ID 885419
The effect of 5,5-diethylbarbituric acid on the biosynthesis of anthracyclines in Streptomyces galilaeus
The course of growth curves with respect to the biosynthesis of anthracyclines was followed in the wild low-producing strain Streptomyces galilaeus JA 3043 and in its mutants G-167 (producing increased quantities of glycosides of epsilon-pyrromycinone) and J-14 (accumulating free epsilon-pyrromycinone). A two-phase type of fermentation (growth phase, production phase) was observed in strains JA 3043 and J-14. The maximum production of anthracyclines occurred only after the end of intense growth of the culture. Two phases of rapid growth separated by a phase of stagnation were observed in strain G-167. The second growth phase proceeded only during late hours of cultivation and was (as compared with the first phase) associated with an intensive biosynthesis of anthracyclines.
- MeSH
- Anti-Bacterial Agents biosynthesis MeSH
- DNA, Bacterial biosynthesis MeSH
- Species Specificity MeSH
- Fermentation MeSH
- Glucose metabolism MeSH
- Glycosides biosynthesis MeSH
- Mutation MeSH
- Naphthacenes biosynthesis MeSH
- Streptomyces genetics growth & development metabolism MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
- DNA, Bacterial MeSH
- Glucose MeSH
- Glycosides MeSH
- Naphthacenes MeSH
Mutants of Streptomyces coeruleorubidus, blocked in the biosynthesis of anthracycline antibiotics of the daunomycine complex, were isolated from the production strains after treatment with UV light, gamma-radiation, nitrous acid, and after natural selection; according to their different biosynthetic activity the mutants were divided into five phenotypic groups. Mutants of two of these groups produced compounds that had not yet been described in Streptomyces coeruleorubidus (aklavinone, 7-deoxyaklavinone, zeta-rhodomycinone and glycosides of epsilon-rhodomycinone). The mutants differed from the parent strains and also mutually in morphological characteristics but no direct correlation between these changes and the biosynthetic activity could be observed in most cases.
- MeSH
- Anthraquinones biosynthesis MeSH
- Daunorubicin biosynthesis MeSH
- Glycosides biosynthesis MeSH
- Mutation MeSH
- Streptomyces cytology genetics metabolism MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anthraquinones MeSH
- Daunorubicin MeSH
- Glycosides MeSH
The production of epsilon-pyrromycinone glycosides in Streptomyces galilaeus increased 12-fold, with respect to the wild strain, as a result of a sequential procedure including both natural selection and treatment with mutagens (nitrous acid, UV light and gamma-irradiation). Nitrous acid exhibited the highest mutagenic effect, both in increasing the productivity and in inducing blocked mutants. A mutant strain blocked in the biosynthesis of glycosides and accumulating free epsilon-pyrromycinone as the principal metabolite was obtained.
- MeSH
- Anthraquinones biosynthesis MeSH
- Glycosides biosynthesis MeSH
- Nitrous Acid pharmacology MeSH
- Mutation drug effects radiation effects MeSH
- Antibiotics, Antineoplastic biosynthesis MeSH
- Streptomyces drug effects genetics metabolism radiation effects MeSH
- Ultraviolet Rays MeSH
- Gamma Rays MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anthraquinones MeSH
- Glycosides MeSH
- Nitrous Acid MeSH
- Antibiotics, Antineoplastic MeSH
Strains of Streptomyces coeruleorubidus ISP 5145, JA 10092 and 39-146, differing mutually in antibiotic activity, were found to produce identical spectrum of metabolites (at least nine antibiotically active glycosides, 13-dihydrodaunomycinone, epsilon-rhodomycinone and a larger number of unidentified compounds); only trace quantities of daunomycin and daunomycinone could be detected. A fraction of glycosides with a higher RF (0.4-0.7), isolated from strain 39-146, could be transformed to daunomycin by mild hydrolysis and to daunomycinone by total hydrolysis. Streptomyces peucetius IMI 101 335 differed from Streptomyces coeruleorubidus in an increased production of epsilon-rhodomycinone and a lower content of glycosides; the zone of daunomycin was most pronounced among the glycoside spots. Streptomyces coeruleorubidus 39-146 exhibited the highest activity in a medium containing 3.5% soluble starch, 3.0% soybean meal, 0.3% NaCl and 0.3% CaCo3; glucose was a more useful carbon source for the remaining strains. The activity of Streptomyces coeruleoribidus was inhibited by 1-propanol, Na-propionate, 5,5-diethylbarbiturate and bacitracin. Ferrous sulphate stimulated the production of glycosides only in strain JA 10092, decreasing simultaneously the production of aglycones.
- MeSH
- Chromatography, Thin Layer MeSH
- Daunorubicin analogs & derivatives biosynthesis isolation & purification MeSH
- Fermentation MeSH
- Glycosides biosynthesis MeSH
- Culture Media MeSH
- Immersion MeSH
- Streptomyces metabolism MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Daunorubicin MeSH
- Glycosides MeSH
- Culture Media MeSH