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

Liu, Lifang,1979Chalmers tekniska högskola,Chalmers University of Technology (author)

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.

Zhang, Yiming,1986Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)yimingz (author)
Liu, Zihe,1984Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)zihe (author)
Petranovic Nielsen, Dina,1975Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)dinap (author)
Nielsen, Jens B,1962Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj (author)
Chalmers tekniska högskola (creator_code:org_t)

In:FEMS Yeast Research: Oxford University Press (OUP)15:7, s. 10-1567-13561567-1364

By the author/editor: Liu, Lifang, 197 ...; Zhang, Yiming, 1 ...; Liu, Zihe, 1984; Petranovic Niels ...; Nielsen, Jens B, ...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Microbiology

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