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Genome-scale metabolic model of Pichia pastoris with native and humanized glycosylation of recombinant proteins
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- Irani, Z. A. (author)
- Tarbiat Modares University
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- Kerkhoven, Eduard, 1985 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Shojaosadati, S. A. (author)
- Tarbiat Modares University
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- (creator_code:org_t)
- 2015-11-02
- 2016
- English.
- In: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 113:5, s. 961-969
- Journal article (peer-reviewed)
Abstract
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- Pichia pastoris is used for commercial production of human therapeutic proteins, and genome-scale models of P. pastoris metabolism have been generated in the past to study the metabolism and associated protein production by this yeast. A major challenge with clinical usage of recombinant proteins produced by P. pastoris is the difference in N-glycosylation of proteins produced by humans and this yeast. However, through metabolic engineering, a P. pastoris strain capable of producing humanized N-glycosylated proteins was constructed. The current genome-scale models of P. pastoris do not address native nor humanized N-glycosylation, and we therefore developed ihGlycopastoris, an extension to the iLC915 model with both native and humanized N-glycosylation for recombinant protein production, but also an estimation of N-glycosylation of P. pastoris native proteins. This new model gives a better prediction of protein yield, demonstrates the effect of the different types of N-glycosylation of protein yield, and can be used to predict potential targets for strain improvement. The model represents a step towards a more complete description of protein production in P. pastoris, which is required for using these models to understand and optimize protein production processes.
Subject headings
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Keyword
- Pichia pastoris
- genome scale metabolic model
- humanized glycosylation
- recombinant protein production
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