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

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 increasi...

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Main Authors: Liu, Lifang, Zhang, Y., Liu, Z., Petranovic, D., Nielsen, J.
Format: Journal Article
Published: 2015
Online Access:http://hdl.handle.net/20.500.11937/33532
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author Liu, Lifang
Zhang, Y.
Liu, Z.
Petranovic, D.
Nielsen, J.
author_facet Liu, Lifang
Zhang, Y.
Liu, Z.
Petranovic, D.
Nielsen, J.
author_sort Liu, Lifang
building Curtin Institutional Repository
collection Online Access
description 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 a-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.
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institution Curtin University Malaysia
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publishDate 2015
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spelling curtin-20.500.11937-335322017-09-13T15:32:01Z Improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in Saccharomyces cerevisiae Liu, Lifang Zhang, Y. Liu, Z. Petranovic, D. Nielsen, J. 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 a-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. 2015 Journal Article http://hdl.handle.net/20.500.11937/33532 10.1093/femsyr/fov070 unknown
spellingShingle Liu, Lifang
Zhang, Y.
Liu, Z.
Petranovic, D.
Nielsen, J.
Improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in Saccharomyces cerevisiae
title Improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in Saccharomyces cerevisiae
title_full Improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in Saccharomyces cerevisiae
title_fullStr Improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in Saccharomyces cerevisiae
title_full_unstemmed Improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in Saccharomyces cerevisiae
title_short Improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in Saccharomyces cerevisiae
title_sort improving heterologous protein secretion at aerobic conditions by activating hypoxia-induced genes in saccharomyces cerevisiae
url http://hdl.handle.net/20.500.11937/33532