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

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