Epothilone is a secondary metabolite of Sorangium cellulosum and a kind of highly effective anti-cancer medicine. However, its yield is very low, which blocks its industrial fermentation production. In this paper, several mutant strains were obtained by NTG mutation with NTG concentration and mutation time being of 300 μg/mL and 30 min, respectively. Finally two high epothilone A-producing strains were obtained and their yields reached 17.30 mg/L and 17.40 mg/L.