Biosynthesis of the antibiotic maduramicin origin of the carbon and oxygen atoms as well as the 13c NMR assignments

Abstract

The biosynthesis of maduramicin a and β in a culture of Actinomadura yumaensis has been studied using 13C, 14C and 13O labeled precursors. The a component of this recently discovered polyether antibiotic, containing forty-seven carbon atoms in a seven-ring system, is derived from eight acetate, seven propionate and four methionine molecules. The β component which is missing one methoxy group incorporates three methionine methyl groups. The carbohydrate moiety was enriched by methionine, but not significantly by acetate or propionate. Studies of the incorporation of 13C labeled precursors permit the 13C NMR assignment of maduramicin. The origin of oxygen atoms of maduramicin has been examined by feeding [1-13C, 13O2]acetate and [l-I3C,13O2]propionate separately in the fermentation culture and the resulting doubly labeled maduramicin samples were analyzed by the isotopic shifts in the I3C NMR spectra. These results are consistent with the initial formation of a triene, which is converted to maduramicin by cyclization of the triepoxide. © 1984, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.