Protein folding and conformational stress in microbial cells producing recombinant proteins: a host comparative overview

Brigitte Gasser¹ , Markku Saloheimo² , Ursula Rinas³ , Martin Dragosits¹ , Escarlata Rodríguez-Carmona⁴ , Kristin Baumann⁵ , Maria Giuliani⁶ , Ermenegilda Parrilli⁶ , Paola Branduardi⁷ , Christine Lang⁸ , Danilo Porro⁷ , Pau Ferrer⁵ , Maria Luisa Tutino⁶ , Diethard Mattanovich¹ and Antonio Villaverde⁴

¹University of Natural Resources and Applied Life Sciences Vienna, Department of Biotechnology, Vienna, Austria

²VTT Technical Research Centre, Espoo, Finland

³Helmholtz Center for Infection Research, Braunschweig, Germany

⁴Autonomous University of Barcelona, Institute for Biotechnology and Biomedicine, Department of Genetics and Microbiology, and CIBER-BBN Network in Bioengineering, Biomaterials and Nanomedicine, Barcelona, Spain

⁵Autonomous University of Barcelona, Department of Chemical Engineering, Barcelona, Spain

⁶University of Naples Federico II, School of Biotechnological Sciences, Naples, Italy

⁷University of Milano-Bicocca, Department of Biotechnology and Bioscience, Milan, Italy

⁸Technical University Berlin, Faculty III, Institute for Microbiology and Genetics, Berlin, Germany

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Microbial Cell Factories 2008, 7:11doi:10.1186/1475-2859-7-11


Published:	4 April 2008

Abstract

Different species of microorganisms including yeasts, filamentous fungi and bacteria have been used in the past 25 years for the controlled production of foreign proteins of scientific, pharmacological or industrial interest. A major obstacle for protein production processes and a limit to overall success has been the abundance of misfolded polypeptides, which fail to reach their native conformation. The presence of misfolded or folding-reluctant protein species causes considerable stress in host cells. The characterization of such adverse conditions and the elicited cell responses have permitted to better understand the physiology and molecular biology of conformational stress. Therefore, microbial cell factories for recombinant protein production are depicted here as a source of knowledge that has considerably helped to picture the extremely rich landscape of in vivo protein folding, and the main cellular players of this complex process are described for the most important cell factories used for biotechnological purposes.