Heat shock response improves heterologous protein secretion in Saccharomyces cerevisiae
Journal article, 2013

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 low due to limitations of the host strain. Heat shock response (HSR) is an inducible, global, cellular stress response, which facilitates the cell recovery from many forms of stress, e.g., heat stress. In S. cerevisiae, HSR is regulated mainly by the transcription factor heat shock factor (Hsf1p) and many of its targets are genes coding for molecular chaperones that promote protein folding and prevent the accumulation of mis-folded or aggregated proteins. In this work, we over-expressed a mutant HSF1 gene HSF1-R206S which can constitutively activate HSR, so the heat shock response was induced at different levels, and we studied the impact of HSR on heterologous protein secretion. We found that moderate and high level over-expression of HSF1-R206S increased heterologous alpha-amylase yield 25 and 70 % when glucose was fully consumed, and 37 and 62 % at the end of the ethanol phase, respectively. Moderate and high level over-expression also improved endogenous invertase yield 118 and 94 %, respectively. However, human insulin precursor was only improved slightly and this only by high level over-expression of HSF1-R206S, supporting our previous findings that the production of this protein in S. cerevisiae is not limited by secretion. Our results provide an effective strategy to improve protein secretion and demonstrated an approach that can induce ER and cytosolic chaperones simultaneously.

Heterologous protein production

Chaperones

Saccharomyces cerevisiae

HSF1

Heat shock response

Author

Jin Hou

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Tobias Österlund

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Zihe Liu

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Dina Petranovic Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Jens B Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Applied Microbiology and Biotechnology

0175-7598 (ISSN) 1432-0614 (eISSN)

Vol. 97 8 3559-3568

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

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

Infrastructure

C3SE (Chalmers Centre for Computational Science and Engineering)

Areas of Advance

Life Science Engineering (2010-2018)

Subject Categories

Chemical Sciences

DOI

10.1007/s00253-012-4596-9

More information

Created

10/8/2017