Simulation and in Silico Analysis of Fed-Batch Feeding Strategy of Pichia Pastoris For the Production of Recombinant Protein Using Systems Biology Approach

Pichia pastoris is recognized as an effective host for recombinant protein production# there is considerable interest in improving recombinant protein production in pichia pastoris through developing feeding strategy in fed-batch cultures which requires a comprehensive understanding of the bottlenecks in the cellular machine as well as the entire cellular network# in this study, recombinant human growth hormone production in pichia pastoris in fed-batch cultivation was investigated# through using methanol-glycerol feeding during induction phase, protein production reached to approximately 700 mgl-1# the biomass profile during induction phase was simulated using dynamic flux balance analysis# most important metabolites during cultivation were identified through flux-sum analyses# it was elucidated that 50% of the metabolites are not utilized in the cell metabolism#