Pilot studies on scale-up biocatalysis of 7-β-xylosyl-10-deacetyltaxol and its analogues by an engineered yeast. (1st June 2015)

• Record Type: Journal Article
• Authors: Liu, Wan-Cang; Zhu, Ping
• Is Part Of: Journal of industrial microbiology & biotechnology. Volume 42:Number 6(2015)
• Page Start: 867
• Page End: 876
• Publication Date: 2015-06-01
• Subjects: Bioconversion -- Scale-up -- Engineered yeast -- 7-β-Xylosyl-10-deacetyltaxol -- Paclitaxel; Industrial microbiology -- Periodicals; 660.62
• DOI: 10.1007/s10295-015-1617-6
• Languages: English
• ISSNs: 1367-5435

Abstract

Abstract: Paclitaxel content in yew tree is extremely low, causing a worldwide shortage of this important anticancer drug. Yew tree can also produce abundant 7-β-xylosyl-10-deacetyltaxol that can be bio-converted into 10-deacetyltaxol for semi-synthesis of paclitaxel. However, the bio-conversion by the screened natural microorganisms was inefficient. We have constructed the recombinant yeast with a glycoside hydrolase gene from Lentinula edodes and explored the bioconversion. Based on previously established reaction conditions, the bioconversion of 7-β-xylosyl-10-deacetyltaxol or its extract was further optimized and scaled up with the engineered yeast harvested from 200-L scale high-cell-density fermentation. The optimization included the freeze-dried cell amount, dimethyl sulfoxide concentration, addition of 0.5 % antifoam supplement, and substrate concentration. A 93–95 % bioconversion and 83 % bioconversion of 10 and 15 g/L 7-β-xylosyltaxanes in 10 L reaction volume were achieved, respectively. The yield of 10-deacetyltaxol reached 10.58 g/L in 1 L volume with 15 g/L 7-β-xylosyl-10-deacetyltaxol. The conversion efficiencies were not only much higher than those of other reports and our previous work, but also realized in 10 L reaction volume. A pilot-scale product purification was also established. Our study bridges the gap between the basic research and commercial utilization of 7-β-xylosyl-10-deacetyltaxol for the industrial production of semi-synthetic paclitaxel.