The Improvement of Epothilone D Yield by the Disruption of epoK Gene in Sorangium cellulosum Using TALEN System.

Epothilones are a kind of 16-member macrolides with strong anticancer activity, which was produced by Sorangium cellulosum. Epothlione D shows better drug resistance and safety than taxol in clinical trials. However, the low yield of epothilone D in Sorangium cellulosum and thereof toxicity limited the application of epothilone D. In this study, the epoK gene in gene cluster for epothilone was firstly inactivated by the employment of TALEN gene knockout system. The qRT-PCR analysis and sequencing were performed to confirm the gene deletion of epoK, resulting in the epothilone D yield improvement by 34.9±1.6% and the decrease of epothilone B yield by 34.2±2.5%, which was demonstrated by LC-MS analysis. This study would lay a foundation for the yield improvement of epothilones D, B and thereof derivatives in S. cellulosum by genetic engineering, thus promoting the applications of epothilones in the field of anticancer.