Biosynthetic Origin of the Oxygen Atoms of Aquayamycin: Aspects for the Biosynthesis of the Urdamycin Family and for Aquayamycin-Containing Angucycline Antibiotics in General

Experiments with ¹⁸O₂ and [l-¹³C,¹⁸O₂]acetate determined the biosynthetic origin of the oxygen atoms of aquayamycin (1), which is the aglycon moiety of the urdamycins A (2, kerriamycin B) and G (3, OM 4842) and the most frequently occurring aglycon among the angucyclines. The fact that 4a-0 derives from acetate and 12b-0 from molecular oxygen leads to the postulation of a biosynthetic scheme, in which a hypothetical tetracyclic compound 9 similar to SF-2315 A (10) and urdamycinone F (7) are key intermediates. Oxygen deficiency experiments with the urdamycin producer Streptomyces fradiae (strain Tü 2717) resulted in the production of only urdamycin B (4), when the oxygen level was reduced gradiently from 20% to 5% during the fermentation process. This result is in conformance with the postulated biosynthesis scheme; i.e., suppression of the 12bmonooxygenase leads to a shunt pathway with 4 being the final product.