Scale up of fed-batch production of rh-GCSF in E .coli

Scale up of the process can change the hydrodynamic conditions of recombinant protein production and reduce productivity in the same operating conditions. Scale up of fermentation process based on geometrical analogy and constant dissolved oxygen concentration as current criteria cansignificantly reduce the decrease of recombinant protein production resulting from scale up. In this study, these two strategies are used to scale up of rh-GCSF production in fed-batch fermentation. The fed-batch fermentation under optimal condition (obtained in the previous stage) was scaled up.Then with strategy of feeding with maximum available specific growth rate without acetate production , scale up of fed-batch process of recombinant E. coli in 13 liters fermenter with working volume of 8 liters based on geometrical analogy and constant dissolved oxygenconcentration was done. By induction at cell density 75 g dry cell weight per liter (gdcw/l),maximum cell density and concentrations of rh-GCSF at 18.5 hours after the start of fermentationwere 116 g dcw/l and 20 g/l obtained, respectively. Plasmid stability at the end of process is 95%.The results indicate that this strategy has been adapted to scale up succesfully. According to available data this is the highest specific yield and productivity that has been reported for recombinant proteins production yet in this scale.

کلیدواژه ها:

Fed-batch culture ، E. coli ، Scale up ، High cell density culture ، Geometrical analogy ، Dissolved oxygen concentration