In the original fermentation process, epothilone A is produced preferentially over epothilone B. The inclusion of XAD-16 resin was found to dramatically improve the epothilone productivity, and also to be useful in the isolation and purification of epothilones. By adding sodium propionate to the fermentation medium, the production of epothilone B is enhanced and produced preferentially over the production of epothilone A. The increase of epothilone B productivity was slow in the original propionate fed fermentation process, indicating some of the nutrient may not be sufficient to sustain the epothilone B productivity. By taking fermentation broth at different time points and spiking the broth with individual medium components, the nutrient requirements at different fermentation time points were established. By supplementing these nutrient components during fermentation, a four to five fold improvement in epothilone B productivity was achieved.