Genome-scale metabolic model of Pichia pastoris with native and humanized glycosylation of recombinant proteins

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.

Kerkhoven, Eduard,1985Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)eduardk (författare)
Shojaosadati, S. A.Tarbiat Modares University (författare)
Nielsen, Jens B,1962Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj (författare)
Tarbiat Modares UniversityChalmers tekniska högskola (creator_code:org_t)

Ingår i:Biotechnology and Bioengineering: Wiley113:5, s. 961-9690006-35921097-0290

Av författaren/redakt...: Irani, Z. A.; Kerkhoven, Eduar ...; Shojaosadati, S. ...; Nielsen, Jens B, ...

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