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Quo vadis? The challenges of recombinant protein folding and secretion in Pichia pastoris

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Abstract

The development of Pichia pastoris as a production platform for recombinant proteins has been a remarkable success story over the last three decades. Stable cheap production processes and the good protein secretion abilities were pacemakers of this development. However, limitations of protein folding, glycosylation or secretion have been identified quite early on. With the availability of genome sequences and the development of systems biology characterization in the last 5 years, remarkable success in strain improvement was achieved. Here, we focus on recent developments of characterization and improvement of P. pastoris production strains regarding protein folding, intracellular trafficking, glycosylation and proteolytic degradation.

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Acknowledgments

Research on Pichia pastoris in our laboratory is supported by the Austrian Science Fund (FWF), the Austrian Research Promotion Agency and by the Federal Ministry of Science, Research and Economy (BMWFW), the Federal Ministry of Traffic, Innovation and Technology (bmvit), the Styrian Business Promotion Agency SFG, the Standortagentur Tirol and ZIT—Technology Agency of the City of Vienna through the COMET-Funding Program managed by the Austrian Research Promotion Agency FFG. Further support by Polymun Scientific GmbH, Biomin Research Center, Boehringer-Ingelheim RCV, Lonza AG, Biocrates Life Sciences AG, VTU Technology GmbH and Sandoz GmbH is acknowledged. We thank the BOKU-VIBT Imaging Center for access to Leica fluorescence microscope devices.

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Authors and Affiliations

  1. Austrian Centre of Industrial Biotechnology, Muthgasse 11, 1190, Vienna, Austria

    Verena Puxbaum, Diethard Mattanovich & Brigitte Gasser

  2. Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190, Vienna, Austria

    Verena Puxbaum, Diethard Mattanovich & Brigitte Gasser

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  1. Verena Puxbaum
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  2. Diethard Mattanovich
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  3. Brigitte Gasser
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Correspondence to Diethard Mattanovich.

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Puxbaum, V., Mattanovich, D. & Gasser, B. Quo vadis? The challenges of recombinant protein folding and secretion in Pichia pastoris . Appl Microbiol Biotechnol 99, 2925–2938 (2015). https://doi.org/10.1007/s00253-015-6470-z

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  • DOI: https://doi.org/10.1007/s00253-015-6470-z

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