Influence of growth temperature on the production of antibody Fab fragments in different microbes: A host comparative analysis

Martin Dragosits, Gianni Frascotti, Lise Bernard-Granger, Felícitas Vázquez, Maria Giuliani, Kristin Baumann, Escarlata Rodríguez-Carmona, Jaana Tokkanen, Ermenegilda Parrilli, Marilyn G. Wiebe, Renate Kunert, Michael Maurer, Brigitte Gasser, Michael Sauer, Paola Branduardi, Tiina Pakula, Markku Saloheimo, Merja Penttilä, Pau Ferrer, Maria Luisa TutinoAntonio Villaverde, Danilo Porro, Diethard Mattanovich

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32 Citations (Scopus)

Abstract

Microorganisms encounter diverse stress conditions in their native habitats but also during fermentation processes, which have an impact on industrial process performance. These environmental stresses and the physiological reactions they trigger, including changes in the protein folding/secretion machinery, are highly interrelated. Thus, the investigation of environmental factors, which influence protein expression and secretion is still of great importance. Among all the possible stresses, temperature appears particularly important for bioreactor cultivation of recombinant hosts, as reductions of growth temperature have been reported to increase recombinant protein production in various host organisms. Therefore, the impact of temperature on the secretion of proteins with therapeutic interest, exemplified by a model antibody Fab fragment, was analyzed in five different microbial protein production hosts growing under steady-state conditions in carbon-limited chemostat cultivations. Secretory expression of the heterodimeric antibody Fab fragment was successful in all five microbial host systems, namely Saccharomyces cerevisiae, Pichia pastoris, Trichoderma reesei, Escherichia coli and Pseudoalteromonas haloplanktis. In this comparative analysis we show that a reduction of cultivation temperature during growth at constant growth rate had a positive effect on Fab 3H6 production in three of four analyzed microorganisms, indicating common physiological responses, which favor recombinant protein production in prokaryotic as well as eukaryotic microbes. © 2010 American Institute of Chemical Engineers.
Original languageEnglish
Pages (from-to)38-46
JournalBiotechnology Progress
Volume27
DOIs
Publication statusPublished - 1 Jan 2011

Keywords

  • Chemostat
  • Escherichia coli
  • Pichia pastoris
  • Pseudoalteromonas haloplanktis
  • Recombinant protein production
  • Saccharomyces cerevisiae
  • Trichoderma reesei

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    Dragosits, M., Frascotti, G., Bernard-Granger, L., Vázquez, F., Giuliani, M., Baumann, K., Rodríguez-Carmona, E., Tokkanen, J., Parrilli, E., Wiebe, M. G., Kunert, R., Maurer, M., Gasser, B., Sauer, M., Branduardi, P., Pakula, T., Saloheimo, M., Penttilä, M., Ferrer, P., ... Mattanovich, D. (2011). Influence of growth temperature on the production of antibody Fab fragments in different microbes: A host comparative analysis. Biotechnology Progress, 27, 38-46. https://doi.org/10.1002/btpr.524