Studies on the biosynthesis of epothilones: the biosynthetic origin of the carbon skeleton.

ABSTRACT

The biosynthetic origin of the epothilone skeleton was studied by the incorporation of 13C and radioactively labeled precursors by Sorangium cellulosum So ce90. The carbon atoms are derived from acetate, propionate, the methyl group of S-adenosyl-methionine, and cysteine which also introduces the sulfur and nitrogen atoms. Epothilone biosynthesis starts with the formation of the thiazole part from acetate and cysteine. The incorporation of acetate or propionate units results in the formation of epothilones A and B, respectively. To introduce the epoxide function of epothilones A and B molecular oxygen is used.