Engineering of vesicle trafficking improves heterologous protein secretion in Saccharomyces cerevisiae
Artikel i vetenskaplig tidskrift, 2012

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.

Heterologous protein secretion

Vesicle trafficking

Saccharomyces cerevisiae

Sec1p

Sly1p

Författare

Jin Hou

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Keith Tyo

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Zihe Liu

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Dina Petranovic Nielsen

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Jens B Nielsen

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Metabolic Engineering

1096-7176 (ISSN) 1096-7184 (eISSN)

Vol. 14 2 120-127

Industrial Systems Biology of Yeast and A. oryzae (INSYSBIO)

Europeiska kommissionen (FP7), 2010-01-01 -- 2014-12-31.

Ämneskategorier

Industriell bioteknik

Styrkeområden

Livsvetenskaper och teknik

DOI

10.1016/j.ymben.2012.01.002