The biosynthetic origin of the epothilone skeleton was studied by the incor
poration of C-13 and radioactively labeled precursors by Sorangium cellulos
um So ce90. The carbon atoms are derived from acetate, propionate, the meth
yl group of S-adenosyl-methionine, and cysteine which also introduces the s
ulfur and nitrogen atoms. Epothilone biosynthesis starts with the formation
of the thiazole part from acetate and cysteine. The incorporation of aceta
te or propionate units results in the formation of epothilones A and B, res
pectively. To introduce the epoxide function of epothilones A and B molecul
ar oxygen is used.