Scaling-up Fermentation of Pichia pastoris to demonstration-scale using new methanol-feeding strategy and increased air pressure instead of pure oxygen supplement

Scientific Reports
Wan-Cang LiuPing Zhu

Abstract

Scaling-up of high-cell-density fermentation (HCDF) of Pichia pastoris from the lab or pilot scale to the demonstration scale possesses great significance because the latter is the final technological hurdle in the decision to go commercial. However, related investigations have rarely been reported. In this paper, we study the scaling-up processes of a recombinant P. pastoris from the pilot (10 to 100-L) to the demonstration (1,000-L) scales, which can be used to convert 7-β-xylosyl-10-deacetyltaxol into 10-deacetyltaxol by the β-xylosidase for semi-synthesis of Taxol. We demonstrated that a pure oxygen supplement can be omitted from the HCDF if the super atmospheric pressure was increased from 0.05 to 0.10 ± 0.05 MPa, and we developed a new methanol feeding biomass-stat strategy (0.035 mL/g/h) with 1% dissolved oxygen and 100 g/L initial induction biomass (dry cell weight). The scaling-up was reproducible, and the best results were obtained from the 1,000-L scale, featuring a shorter induction time and the highest enzyme activities and productions, respectively. The specific growth and specific production rates were also determined. This study lays a solid foundation for the commercial preparation of 10-deacetyltaxol through t...Continue Reading

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Citations

Dec 7, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jing-Jing ChenPing Zhu
Jan 3, 2019·Critical Reviews in Biotechnology·Wan-Cang LiuPing Zhu
Dec 28, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jing-Jing ChenPing Zhu
Jul 9, 2020·World Journal of Microbiology & Biotechnology·Jin-Ling YangPing Zhu
Mar 4, 2021·Nature Communications·Sierra M Brooks, Hal S Alper

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Datasets Mentioned

BETA
AET31459
JN167171

Software Mentioned

Quantity One
stat
SPSS
DO

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