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Bioprocess and Biosystems Engineering

, Volume 25, Issue 4, pp 255–262 | Cite as

Model-based optimization of viral capsid protein production in fed-batch culture of recombinant Escherichia coli

  •  D. Levisauskas
  •  V. Galvanauskas
  •  S. Henrich
  •  K. Wilhelm
  •  N. Volk
  •  A. Lübbert
Original Paper

Abstract.

An optimized fed-batch cultivation process for the production of the polyoma virus capsid protein VP1 in recombinant Escherichia coli BL21 bacteria is presented. The optimization procedure maximizing the amount of desired protein is based on a mathematical model. The model distinguishes an initial cell growth phase from a protein production phase initiated by inducer injection. A new approach to model the target protein formation rate was elaborated, where product formation is primarily dependent on the specific biomass growth rate. Lower growth rates led to higher specific protein concentrations. The model was identified from a series of fed-batch experiments designed for parameter identification purposes and possesses good prediction quality. Then the model was used to determine optimal open-loop control profiles by manipulating the substrate feed rates in both phases as well as the induction time. Feed-rate optimization has been solved using Pontryagin's maximum principle. The solution was validated experimentally. A significant improvement of the process performance index was achieved.

Model-based optimization Model for recombinant protein production Pontryagin's maximum principle Fed-batch Escherichia coli cultivation Virus capsid protein 

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  •  D. Levisauskas
    • 1
  •  V. Galvanauskas
    • 1
  •  S. Henrich
    • 2
  •  K. Wilhelm
    • 2
  •  N. Volk
    • 2
  •  A. Lübbert
    • 2
  1. 1.Process Control Department, Kaunas University of Technology, Studentu 50, 3028 Kaunas, Lithuania
  2. 2.Institute of Bioengineering, Martin-Luther University, Halle-Wittenberg, 06099 Halle/Saale, Germany

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