Production of Recombinant Proteins with Pichia pastoris in Integrated Processing

Authors

  • G. Cornelissen,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • H.-P. Bertelsen,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • K. Lenz,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • B. Hahn,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • M. Schultz,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • U. Scheffler,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • E. Werner,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • H. Leptien,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • S. Krüß,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • A.-K. Jansen,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • O. Elsholz,

    1. Research Center of Bioprocess Engineering and Analytical Techniques, Department of Natural Sciences, Hamburg University of Applied Sciences, Lohbrügger Kirchstr. 65, D-21033 Hamburg, Germany
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  • T. Gliem,

    1. B. Braun Biotech International (BBI) – Sartorius Group, Schwarzenberger Weg 73–79, D-34212 Melsungen, Germany
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    • http://www.bbraunbiotech.com

  • B.-U. Wilhelm,

    1. B. Braun Biotech International (BBI) – Sartorius Group, Schwarzenberger Weg 73–79, D-34212 Melsungen, Germany
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  • E. Sowa,

    1. Clinical Center of Johann-Wolfgang-Goethe University, Pharma Center Frankfurt, Institute of Pharmacology and Toxicology, Theodor-Stern-Kai 7, D-60590 Frankfurt a. M., Germany
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  • H.H. Radeke,

    1. Clinical Center of Johann-Wolfgang-Goethe University, Pharma Center Frankfurt, Institute of Pharmacology and Toxicology, Theodor-Stern-Kai 7, D-60590 Frankfurt a. M., Germany
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    • http://www.radeke.de

  • R. Luttman

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    • http://www.rzbd.haw-hamburg.de/~fsbpa


Abstract

Devices and methods for Integrated Bioprocessing have been developed for production of recombinant proteins with the yeast Pichia pastoris. In doing so cross flow filtration techniques for cell separation and product concentration are connected directly to high instrumented cultivation processes. These are equipped with on-line measuring techniques for substrates and products, e.g., glycerol, methanol and pyruvate as well as recombinant proteins, e.g., the chemokines 1–8del MCP-1 and vMIP-II. Complex automation structures allow for process development at virtual plants which can be used as the basis for establishing and implementing fully automated real processes. Experiments for determination of reaction kinetics, optimization of productivity in high-cell density cultures and Integrated Bioprocessing are outlined, along with detailed illustration of the realization of the methods at industrial pilot plant scale.

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