Production of Thailandepsin a from burkholderia thailandensis E264/pBMTL3-tdpR fermentation

The wild strain of Burkholderia thailandensis E264 can produce Thailandepsin A which is a promising anti-cancer drug. Based on positive regulation of tdpR, agenetic engineered strain of Burkholderia thailandensis E264/pBMTL3-tdpR was constructed to improve the yield of Thailandepsin A. An optimized culturing condition was obtained as: glucose and tryptone as carbon and nitrogen sources, respectively; medium volume 65/250 mL; inoculum ratio 1%; induction by 0.5% lactose for 6 h after culturing for 15 h. After further optimization of the fermentation media, the yield of Thailandepsin A was 252.14 mg·L^-1 which increased over 56% in comparison with the control. In addition, macroporous resin HP-20 was added to adsorb Thailandepsin A in the fermentation, and the yield of Thailandepsin A reached 283.75 mg·L^-1, which increased 13.8% comparing that without HP-20. RT-PCR and the Ct value method were used to compare the genetic engineered strain with the wild strain, and the results show that tdpB and tdpC1 of the genetic engineered strain were enhanced 11.4 and 6.0 times respectively, and the yield of Thailandepsin A was enhanced 4.6 times, which indicates that the over expression of regulatory gene tdpR promoted the transcription of biosynthetic genes and the production.