TY - JOUR
T1 - Engineering of vesicle trafficking improves heterologous protein secretion in Saccharomyces cerevisiae
AU - Hou, Jin
AU - Tyo, Keith
AU - Liu, Zihe
AU - Petranovic, Dina
AU - Nielsen, Jens
N1 - Funding Information:
We thank The Knut and Alice Wallenberg Foundation, EU Framework VII project SYSINBIO (Grant no. 212766 ), European Research Council project INSYSBIO (Grant no. 247013 ), the Chalmers Foundation, and NIH F32 Kirschstein NRSA fellowship for funding support.
PY - 2012/3
Y1 - 2012/3
N2 - 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 Sec1/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 α-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 α-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.
AB - 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 Sec1/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 α-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 α-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.
KW - Heterologous protein secretion
KW - Saccharomyces cerevisiae
KW - Sec1p
KW - Sly1p
KW - Vesicle trafficking
UR - http://www.scopus.com/inward/record.url?scp=84862781268&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862781268&partnerID=8YFLogxK
U2 - 10.1016/j.ymben.2012.01.002
DO - 10.1016/j.ymben.2012.01.002
M3 - Article
C2 - 22265825
AN - SCOPUS:84862781268
SN - 1096-7176
VL - 14
SP - 120
EP - 127
JO - Metabolic Engineering
JF - Metabolic Engineering
IS - 2
ER -