BIOSYNTHETIC ORIGIN OF THE CARBON SKELETON AND OXYGEN ATOMS OF THE LL-F28249α, A POTENT ANTIPARASITIC MACROLIDE

The biosynthesis of LL-F28249α in a culture of Streptomyces cyaneogriseus has been studied using 13C, 14C and 18O labeled precursors. A complete 13C NMR spectrum of F28249α has been assigned. Incorporation studies using 13C labeled precursors indicate that the carbon skeleton of F28249α is derived from seven acetate, six propionate and one 2-methylpropionate units. The origin of the oxygen atoms of F28249α has been examined by feeding [1-13C, 18O2]acetate, [1-13C, 18O2]propionate, [2-13C]acetate/18O2 and 18O2 separately to the fermentation culture and analyzing the resulting labeled LL-F28249α samples by 13C NMR, electron impact MS and chemical ionization MS. Out of a total of eight oxygen atoms in LL-F28249α, four oxygen atoms are derived from acetate, three from propionate and one from molecular oxygen.