Engineering of vesicle trafficking improves heterologous protein secretion in Saccharomyces cerevisiae
Journal article, 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

Author

Jin Hou

Chalmers, Chemical and Biological Engineering, Life Sciences

Keith Tyo

Chalmers, Chemical and Biological Engineering, Life Sciences

Zihe Liu

Chalmers, Chemical and Biological Engineering, Life Sciences

Dina Petranovic Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences

Jens B Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences

Metabolic Engineering

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

Vol. 14 2 120-127

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

European Commission (EC) (EC/FP7/247013), 2010-01-01 -- 2014-12-31.

Subject Categories

Industrial Biotechnology

Areas of Advance

Life Science Engineering (2010-2018)

DOI

10.1016/j.ymben.2012.01.002

More information

Created

10/7/2017