The introduction of the epothilone polyketide synthase (PKS) into Myxococcus xanthus has enabled the heterologous production of epothilone D (1) on a large scale. To isolate this valuable product from the fermentation medium, an economical, scalable, and high-yielding purification process was developed. With the crystallization of 1 from a binary solvent system that consisted of ethanol and water, the product was recovered as white crystals with a final purity of > or =97% (w/w). This is the first reported crystallization of 1.