Stress in recombinant protein producing yeasts

Journal of Biotechnology
Diethard MattanovichMichael Sauer

Abstract

It is well established today that heterologous overexpression of proteins is connected with different stress reactions. The expression of a foreign protein at a high level may either directly limit other cellular processes by competing for their substrates, or indirectly interfere with metabolism, if their manufacture is blocked, thus inducing a stress reaction of the cell. Especially the unfolded protein response (UPR) in Saccharomyces cerevisiae (as well as some other yeasts) is well documented, and its role for the limitation of expression levels is discussed. One potential consequence of endoplasmatic reticulum folding limitations is the ER associated protein degradation (ERAD) involving retrotranslocation and decay in the cytosol. High cell density fermentation, the typical process design for recombinant yeasts, exerts growth conditions that deviate far from the natural environment of the cells. Thus, different environmental stresses may be exerted on the host. High osmolarity, low pH and low temperature are typical stress factors. Whereas the molecular pathways of stress responses are well characterized, there is a lack of knowledge concerning the impact of stress responses on industrial production processes. Accordingly,...Continue Reading

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Citations

Oct 20, 2006·Applied Microbiology and Biotechnology·Leonardo M DamascenoCarl A Batt
Oct 31, 2009·Applied Microbiology and Biotechnology·Mónica Martínez-AlonsoAntonio Villaverde
Feb 9, 2010·Applied Microbiology and Biotechnology·Alimjan IdirisKaoru Takegawa
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