Biosynthesis of the macrotetrolide antibiotics; the incorporation of carbon-13 and oxygen-18 labelled acetate, propionate, and succinate

Abstract

The biosynthesis of the macrotetrolide antibiotics, in particular nonactin, has been studied using carbon-13 and oxygen-18 enriched acetate and propionate, as well as carbon-13 enriched succinate, in feeding experiments with the producing organism Streptomyces griseus. A protocol is described which allows the separation of derivatives formed from each enantiomer of nonactic and homononactic acids. From a study of the incorporation of the labelled precursors into these derivatives it could be shown that the origins of the carbon and oxygen atoms in each enantiomer are identical. The carbon backbone of nonactic acid is assembled from two acetate, one succinate, and one propionate units, and the C–O bonds at C-8, C-6, and C-1 are derived intact from the primary precursors. Based on these data a new proposal is made to account for the biosynthesis of (±)-nonactate, and nonactin, in S, griseus.