Biotransformation of aklanonic acid by blocked mutants of anthracycline-producing strains of Streptomyces galilaeus and Streptomyces peucetius.
Aklanonic acid is an anthracyclinone-related pigment that was found to be an intermediate at an early stage of the biosynthesis of daunomycinone glycosides by Streptomyces griseus. We now isolated anthracycline-negative mutants of other Streptomyces species and used them in feeding experiments with both natural and radioactive aklanonic acid. In cultures of the mutant Streptomyces galilaeus S 727 exogenous aklanonic acid was biotransformed to cinerubin A as the major product. The spectrum of the conversion products was qualitatively comparable to that of the parent strain. In cultures of mutant 21/8 derived from Streptomyces peucetius var. caesius the predominant conversion product was epsilon-rhodomycinone. Daunomycinone glycosides were isolated in small amounts. According to results obtained with the radioactively labelled precursor aklanonic acid was completely incorporated into the molecules of the conversion products. Our findings suggest that aklanonic acid is also a natural intermediate in the biosynthesis of anthracyclines by Streptomyces galilaeus and Streptomyces peucetius. Proposed biosynthetic pathways have been constructed.
Schumann
G
G
Stengel
C
C
Eckardt
K
K
Ihn
W
W
D018943:Anthracyclines; D000880:Anthraquinones / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D000903:Antibiotics, Antineoplastic; D001711:Biotransformation; D009154:Mutation; D009279:Naphthacenes / Q000096:biosynthesis; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
D018943:Anthracyclines; D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; C015490:rhodomycinone; C000481:cinerubine A; C042374:aklanonic acid; C019318:daunomycinone