Modeling And Optimization Of Recombinant Pichia Pastoris Cultivation

In the last decades, the methylotrophic yeast Pichia pastoris has been developed as a prominent host for foreign proteins because of its competitive features. Pichia expression systems have many advantages: strong methanol-induced alcohol oxidase (AOX1) promoter, lack of endotoxins which makes produced protein suitable for therapeutic use, correct folding and secretion of foreign proteins into the medium. Hundreds of foreign proteins have been expressed by Pichia pastoris. Although the expression level of a recombinant protein is mainly depended on the inherent properties of vectors, enhancement of productivity can also be made by optimizing the cultivation medium, or by improving the cultivation methodology. In this dissertation, modeling and process optimization in the cultivation of Pichia pastoris expressing recombinant human serum albumin (rHSA) are studied, and some experimental phenomena in fermentation are detailed as well. The following contents are included in this dissertation.Macrokinetic model for Pichia pastorisBased on the analysis of the metabolic pathways of glycerol and methanol in Pichia...