Simulation and in silico analysis of fed-batch feeding strategy of Pichia pastoris for the production of recombinant protein using systems biology approach
Volume Title: 1
Authors
11Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box 14115 143, Tehran, Iran.
2Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box 14115 143, Tehran, Iran.
3Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box 14115- 143, Tehran, Iran.
Abstract
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.
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