ABSTRACT
One of the important strategies for improving recombinant protein expression in Pichia pastoris is optimizing control during the high density fermentation process. Some fermentation control has been used and got obviously higher expression level:optimization of basal salt medium composition; using two stage pH and two stage temperature control during cell growth and induction stage; appropriately increasing dissolved oxygen; selecting optimal cell density prior to induction (CWPTI) and specific growth rate prior to induction (?PTI),using limit amount of initial glycerolin the basic media and feeding it during the fermentation with exponential fed-batch Model,selecting appropriate methanol feeding strategy by methanol-limited feeding batch (MLFB),oxygen-limited feeding batch (OLFB),methanol-unlimited feeding batch (MNLFB) or temperature-limited feeding batch (TLFB). Some research suggested that the expression level of the recombinant protein increase 9 times after optimizing the fermentation control.