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Engineering of vesicle trafficking improves heterologous protein secretion in Saccharomyces cerevisiae

Jin Hou (Institutionen för kemi- och bioteknik, Systembiologi) ; Keith Tyo (Institutionen för kemi- och bioteknik, Systembiologi) ; Zihe Liu (Institutionen för kemi- och bioteknik, Systembiologi) ; Dina Petranovic (Institutionen för kemi- och bioteknik, Systembiologi) ; Jens B. Nielsen (Institutionen för kemi- och bioteknik, Systembiologi)
Metabolic Engineering (1096-7176). Vol. 14 (2012), 2, p. 120-127.
[Artikel, refereegranskad vetenskaplig]

The yeast Saccharomyces cerevisiae is a widely used platform for the production of heterologous proteins of medical or industrial interest. However, heterologous protein productivity is often restricted due to the limitations of the host strain. In the protein secretory pathway, the protein trafficking between different organelles is catalyzed by the soluble NSF (N-ethylmaleimide-sensitive factor) receptor (SNARE) complex and regulated by the Secl/Munc18 (SM) proteins. In this study, we report that over-expression of the SM protein encoding genes SEC1 and SLY1, improves the protein secretion in S. cerevisiae. Engineering Sec1p, the SM protein that is involved in vesicle trafficking from Golgi to cell membrane, improves the secretion of heterologous proteins human insulin precursor and alpha-amylase, and also the secretion of an endogenous protein invertase. Enhancing Sly1p, the SM protein regulating the vesicle fusion from endoplasmic reticulum (ER) to Golgi, increases alpha-amylase production only. Our study demonstrates that strengthening the protein trafficking in ER-to-Golgi and Golgi-to-plasma membrane process is a novel secretory engineering strategy for improving heterologous protein production in S. cerevisiae.

Nyckelord: Vesicle trafficking, Sec1p, Sly1p, Heterologous protein secretion, Saccharomyces cerevisiae

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Denna post skapades 2012-04-23. Senast ändrad 2016-07-12.
CPL Pubid: 156980


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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Systembiologi (2008-2014)


Industriell bioteknik

Chalmers infrastruktur



Denna publikation är ett resultat av följande projekt:

Industrial Systems Biology of Yeast and A. oryzae (INSYSBIO) (EC/FP7/247013)