Enhanced production of epothilones by carbon sources in Sorangium cellulosum

To improve epothilones production and the ratio of epothilone B/A, carbon sources were investigated in flask culture of Sorangium cellulosum. Depending on the initial concentration, starch significantly enhanced cell growth, but the maximum epothilones productivity and the maximum epothilones production (0.3 mg/l · day and 2.6 mg/l at 15 g/l starch, respectively) were relatively low compared with cell growth. On the other hand, addition of glycerol did not stimulate cell growth, but epothilone production was increased from 2.81 mg/l to 7.59 mg/l. Addition of glycerol to culture medium resulted in more significant enhancement of the production of epothilone A, whereas epothilone B levels were relatively constant. Furthermore, when sodium propionate was added as a precursor of methylmalonyl-CoA, it resulted in increase of both total epothilones production and epothilone B/A resolution. Maximum epothilone A and B concentrations reached 10.9 mg/l and 8.58 mg/l, respectively, at 5 mM sodium propionate.