Biosynthesis of anthracyclines in Streptomyces galilaeus during submerged cultivation is considerably influenced by aeration and by the concentration of glucose in the medium. At higher values of oxygen absorption rate both the production of epsilon-pyrromycinone glycosides in the wild strain JA 3043 and its production mutant G-167 and accumulation of free epsilon-pyrromycinone in the blocked mutant G-162 were found to be higher; the production of 7-deoxyaglycones was lower in all strains. The studied strains differed in the rate of glucose consumption and in the ability to utilize starch for the biosynthesis of anthracyclines. A two-fold concentration of glucose in the medium resulted in the G-162 strain in an increase of the yield of epsilon-pyrromycinone by 120%. The production of glycosides in strain G-167 increased even after exhaustion of glucose from the medium and the amount of 7-deoxyaglycones simultaneously decreased.

• MeSH
• Anti-Bacterial Agents biosynthesis   MeSH
• Fermentation MeSH
• Glucose metabolism   MeSH
• Glycosides biosynthesis   MeSH
• Oxygen * MeSH
• Mutation MeSH
• Naphthacenes biosynthesis   MeSH
• Starch metabolism   MeSH
• Streptomyces genetics   metabolism   MeSH
• Carbon metabolism   MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Glucose MeSH
• Glycosides MeSH
• Oxygen * MeSH
• Naphthacenes MeSH
• Starch MeSH
• Carbon MeSH

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

Cosynthesis of anthracycline compounds was followed in five phenotypic groups of mutants of Streptomyces coeruleorubidus (A--E), blocked in the biosynthesis of the daunomycine complex, and in two mutant types of Streptomyces galilaeus (F, G) blocked in the biosynthesis of glycosides of epsilon-pyrromycinone and aklavinone. Glycosides of daunomycinone and 13-dihydrodaunomycinone were produced in combinations A+B, A+C, A+D, A+E and A+F, epsilon-rhodomycinone was synthesized in combinations A+E, A+F, B+E and B+F. During the cultivation of types B--E with type G or F non-anthracycline compounds, typical of S. galilaeus, were cosynthesized. No cosynthesis could be observed in other combinations of the mutant types. Negative results were also obtained with combinations of mutants of the same group and during cultivation of all mutant types with streptomycetes not producing anthracyclines. A scheme illustrating metabolic pathways leading to the biosynthesis of daunomycinone, aklavinone, epsilon-rhodomycinone in S. coeruleorubidus and S. galilaeus was constructed.

• MeSH
• Daunorubicin analogs & derivatives   biosynthesis   MeSH
• Mutation MeSH
• Streptomyces metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Daunorubicin MeSH

The ability to transorm biologically exogenous daunomycinone, 13-dihydrodaunomycinone, aklavinone, 7-deoxyaklavinone, epsilon-rhodomycinone, epsilon-isorhodomycinone and epsilon-pyrromycinone was studied in submerged cultures of the following strains: wild Streptomyces coeruleorubidus JA 10092 (W1) and its improved variants 39-146 and 84-17 (type P1) producing glycosides of daunomycinone and of 13-dihydrodaunomycinone, together with epsilon-rhodomycinone, 13-dihydrodaunomycinone and 7-deoxy-13-dihydrodaunomycinone; in five mutant types of S. coeruleorubidus (A, B, C, D, E) blocked in the biosynthesis of glycosides and differing in the production of free anthracyclinones; in the wild Streptomyces galilaeus JA 3043 (W2) and its improved variant G-167 (P2) producing glycosides of epsilon-pyrromycinone and of aklavinone together with 7-deoxy and bisanhydro derivatives of both aglycones; in two mutant types S. galilaeus (F and G) blocked in biosynthesis of glycosides and differing in the occurrence of anthracyclinones. The following bioconversions were observed: daunomycinone leads to 13-dihydrodaunomycinone and 7-deoxy-13-dihydrodaunomycinone (all strains); 13-dihydrodaunomycinone leads to 7-deoxy-13-dihydrodaunomycinone (all strains); daunomycinone or 13-dihydrodaunomycinone leads to glycosides of daunomycinone and of 13-dihydrodaunomycinone, identical with metabolites W1 and P1 (type A), or only a single glycoside of daunomycinone (type E); aklavinone leads to epsilon-rhodomycinone (types A and B); aklaviinone leads to 7-deoxyaklavinone and bisanhydroaklavinone (type C); epsilon-rhodomycinone leads to zeta-rhodomycinone (types C, E); epsilon-rhodomycinone leads to glycosides of epsilon-rhodomycinone (types W2, P2); epsilon-isorhodomycinone leads to glycosides of epsilon-isorhodomycinone (types W2, P2); epsilon-pyrromycinone leads to a glycoside of epsilon-pyrromycinone (types W1, P1). 7-Deoxyaklavinone remained intact in all tests. Exogenous daunomycinone suppressed the biosynthesis of its own glycosides in W1 and P1; it simultaneously increased the production of epsilon-rhodomycinone in P1.

• MeSH
• Biotransformation MeSH
• Daunorubicin analogs & derivatives   metabolism   MeSH
• Streptomyces metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Daunorubicin 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

When improving Streptomyces coeruleorubidus JA 10092, a producer of antibiotics of the daunomycinone complex, the most active variants were found among isolates of morphological types bld-1 (with a suppressed production of the aerial mycelium on organic media containing glucose) and whi (with an asporogenic aerial mycelium on glucose media and with the bald phenotype on media containing starch). Submerged cultures of the whi mutants produced increased quantities of daunomycinone glycosides in the antibiotic complex, the amount of free anthracyclinones being simultaneously decreased. The whi strains differed from the wild type also in higher demands for aeration, concentration of glucose and in an increased production capacity in starch media. The overall antibiotic activity increased more than 40 times after a six-step selection (application of UV light, gamma-radiation, nitrous acid and natural spreads) combined with an altered fermentation technology.

• MeSH
• Daunorubicin biosynthesis   MeSH
• Culture Media MeSH
• Mutation MeSH
• Streptomyces cytology   genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Daunorubicin MeSH
• Culture Media MeSH

Variability in the production of nogalamycin by Streptomyces nogalater var. nogalater was followed in untreated and mutagenized populations of the standard strain NRRL 3035 and its spontaneous variant K-18 using the method of agar blocks with subsequent tests under submerged conditions. In both strains the most active variants were obtained by natural selection without mutagenic treatment; in this way productivity increased by 108% after two selection steps. Treatment with UV-radiation did not yield variants with a highly increased activity. Gamma-radiation extended the variability but, at the same, substantially increased the number of non-producing and low-producing isolates. Relatively high yields of (+)-variants were obtained after treatment with nitrous acid but their activity did not reach that observed in the most active spontaneous variants.

• MeSH
• Bacteriological Techniques MeSH
• Culture Media MeSH
• Naphthacenes biosynthesis   MeSH
• Nogalamycin biosynthesis   isolation & purification   MeSH
• Immersion MeSH
• Streptomyces metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Culture Media MeSH
• Naphthacenes MeSH
• Nogalamycin MeSH