Most cited article - PubMed ID 456946
Biotransformations of anthracyclinones in Streptomyces coeruleorubidus and Streptomyces galilaeus
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
- Biotransformation MeSH
- Daunorubicin biosynthesis history MeSH
- History, 20th Century MeSH
- Mutation MeSH
- Antibiotics, Antineoplastic biosynthesis history MeSH
- Streptomyces genetics metabolism MeSH
- Check Tag
- History, 20th Century MeSH
- Publication type
- Journal Article MeSH
- Historical Article MeSH
- Review MeSH
- Comparative Study MeSH
- Names of Substances
- Daunorubicin MeSH
- Antibiotics, Antineoplastic MeSH
Semisynthetic derivatives of daunomycinone with 7,9-isopropylacetal, 7-O-methyl, 7-O-(4-penten-2-yl), and 7-O-(2-hydroxyethyl) substituents were converted by Streptomyces peucetius var. caesius (an adriamycin-blocked mutant) into 7-deoxy-13-dihydrodaunomycinone, while daunomycinone was transformed into 13-dihydrodaunomycinone (predominantly) and 7-deoxy-13-dihydrodaunomycinone. S. coeruleorubidus mutants 24-74 (accumulating aclavinone derivatives instead of daunomycin and related compounds) and 96-85 (producing no anthracycline substances), and S. aureofaciens B-96 (a tetracycline-blocked mutant) transformed the above substrates into the corresponding 13-dihydro derivatives, with the exception of 7,9-isopropylacetal daunomycinone which remained intact. 7-O-Propyn-1-yl daunomycinone was not transformed by any of the strains used under the conditions.
- MeSH
- Naphthacenes metabolism MeSH
- Streptomycetaceae metabolism MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- daunomycinone MeSH Browser
- 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