Urdamycins, new angucycline antibiotics from streptomyces fradiae: IV. Biosynthetic studies of urdamycins A-D

The biogenetic origin of the angucycline antibiotics urdamycins A-D was studied by feeding experiments with isotope labeled precursors and by NMR analysis. Feeding experiments with [1-¹³C]acetate and [1, 2-¹³C2]acetate show that the chromophores of urdamycins A and B and the angucycline 4-ring skeleton of the urdamycins C and D chromophores are formed from a single decapolyketide chain. The chromophores of the urdamycins C and D contain additional structural elements which derived from the amino acids tyrosine and tryptophan, respectively. The latter was shown by feeding deuterium-labeled tyrosine and 13C-labeled tryptophan derivatives. Feeding of [1-¹³C]glucose and of [U-¹³C₃]glycerol proved that the C-glycosidic moiety and the three sugars (2 × L-rhodinose, 1 × D-olivose each) of the urdamycins arise from glucose. Experiments with ¹⁴C-labeled urdamycin A, obtained by biosynthesis from [¹⁴C]acetate, showed this compound to be a late precursor of the urdamycins C and D.