Investigations on the Biosynthesis of the Angucycline Group Antibiotics Aquayamycin and the Urdamycins A and B. Results from the Structural Analysis of Novel Blocked Mutant Products

In order to investigate mid and early biosynthetic steps of angucycline group antibiotics, approximately 400 mutants of the urdamycin producer Streptomyces fradiae (strain Tü 2717) were prepared, of which ca. 10% were selected for further investigations. The selection criterion, i.e., the consideration of only pale-colored metabolite-producing blocked mutants, yielded several mutants whose block was in close proximity to the known late-stage biosynthetic steps. The product patterns were characterized by TLC and HPLC methods, and the structures of five new and one known (but previously not detectable) metabolites were elucidated (3–8). Their roles in the biosynthetic pathway leading to aquayamycin (1) and on to the urdamycins A (2) and B (9) are proposed. The glycosylation sequence of the urdamycin group and two additional earlier biosynthetic steps leading to aquayamycin (1), the most important angucyclinone, were established in this way.