Improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in Saccharomyces cerevisiae
Journal article, 2015

Oxygen is important for normal aerobic metabolism, as well as for protein production where it is needed for oxidative protein folding. However, several studies have reported that anaerobic conditions seem to be more favorable in terms of recombinant protein production. We were interested in increasing recombinant protein production under aerobic conditions so we focused on Rox1p regulation. Rox1p is a transcriptional regulator, which in oxidative conditions represses genes induced in hypoxia. We deleted ROX1 and studied the effects on the production of recombinant proteins in Saccharomyces cerevisiae. Intriguingly, we found a 100% increase in the recombinant fungal alpha-amylase yield, as well as productivity. Varied levels of improvements were also observed for the productions of the human insulin precursor and the yeast endogenous enzyme invertase. Based on the genome-wide transcriptional response, we specifically focused on the effect of UPC2 upregulation on protein production and suggested a possible mechanistic explanation.

ROX1

lipid classes

alpha-amylase

UPC2

Author

Lifang Liu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Yiming Zhang

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Zihe Liu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Dina Petranovic Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

FEMS Yeast Research

1567-1356 (ISSN) 1567-1364 (eISSN)

Vol. 15 7 10-

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

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

Subject Categories

Microbiology

Areas of Advance

Life Science Engineering (2010-2018)

DOI

10.1093/femsyr/fov070

More information

Created

10/7/2017