The growing need of highly potent anticancer agents has stimulated the investigation of streptomycetes producing daunomycin-type anthracyclines. This review compares the features of production strains and their mutants and emphasizes the necessity of application of biochemical and biophysical analytical methods for better understanding these microorganisms and, above all, their further improving and practical usage.

• MeSH
• biotransformace MeSH
• daunomycin biosyntéza   dějiny   MeSH
• dějiny 20. století MeSH
• mutace MeSH
• protinádorová antibiotika biosyntéza   dějiny   MeSH
• Streptomyces genetika   metabolismus   MeSH
• Check Tag
• dějiny 20. století MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• přehledy MeSH
• srovnávací studie MeSH
• Názvy látek
• daunomycin MeSH
• protinádorová antibiotika MeSH

Substances studied at this department in 1954-1983 are reviewed; a total of 226 compounds are characterized in a tabular form. They include natural compounds as well as those prepared by biotransformation, by semisynthetic and synthetic methods.

• MeSH
• antibakteriální látky izolace a purifikace   MeSH
• mikrobiologie MeSH
• organická chemie * MeSH
• pojmy organické chemie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky 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
• biotransformace MeSH
• daunomycin analogy a deriváty   metabolismus   MeSH
• Streptomyces metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• daunomycin 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
• anthrachinony biosyntéza   MeSH
• daunomycin biosyntéza   MeSH
• glykosidy biosyntéza   MeSH
• mutace MeSH
• Streptomyces cytologie   genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anthrachinony MeSH
• daunomycin MeSH
• glykosidy 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
• daunomycin biosyntéza   MeSH
• kultivační média MeSH
• mutace MeSH
• Streptomyces cytologie   genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• daunomycin MeSH
• kultivační média MeSH