A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism
| Autor: | Juergen Zanghellini, Jae Seong Lee, Yingxiang Huang, Daniel C. Zielinski, Daniel Ley, Shangzhong Li, Camila A. Orellana, Philipp Spahn, Bernhard O. Palsson, Nathan E. Lewis, Lasse Ebdrup Pedersen, David E. Ruckerbauer, Sarantos Kyriakopoulos, Natalia E Jiménez, Mikael Rørdam Andersen, Deniz Baycin-Hizal, Veronica Martinez, Kok Siong Ang, Lake-Ee Quek, Zachary A. King, Aarash Bordbar, Harish Nagarajan, Nicole Borth, Helene Faustrup Kildegaard, Anne Mathilde Lund, Dong-Yup Lee, Jahir M. Gutierrez, Alyaa M. Abdel-Haleem, Tune Wulff, Ziomara P. Gerdtzen, Bjørn G. Voldborg, Lars K. Nielsen, Giuseppe Paglia, Alex Thomas, Hooman Hefzi, Meiyappan Lakshmanan, Michael Hanscho, Michael J. Betenbaugh, Johnny Arnsdorf, Nicolás Loira |
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| Přispěvatelé: | Hefzi, H, Ang, K, Hanscho, M, Bordbar, A, Ruckerbauer, D, Lakshmanan, M, Orellana, C, Baycin-Hizal, D, Huang, Y, Ley, D, Martinez, V, Kyriakopoulos, S, Jimenez, N, Zielinski, D, Quek, L, Wulff, T, Arnsdorf, J, Li, S, Lee, J, Paglia, G, Loira, N, Spahn, P, Pedersen, L, Gutierrez, J, King, Z, Lund, A, Nagarajan, H, Thomas, A, Abdel-Haleem, A, Zanghellini, J, Kildegaard, H, Voldborg, B, Gerdtzen, Z, Betenbaugh, M, Palsson, B, Andersen, M, Nielsen, L, Borth, N, Lee, D, Lewis, N |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system Histology Consensus Protein Conformation CHO Systems biology Metabolic network Bioengineering CHO Cells Biology Protein Engineering Article Pathology and Forensic Medicine 03 medical and health sciences Cricetulus metabolic network Protein Phosphatase 1 Cricetinae genome-scale model Protein biosynthesis Animals Humans Bioprocess Gene Secretory pathway Genetics Genome biotherapeutic protein production Chinese hamster ovary cell systems biology Cell Biology Chinese hamster ovary Recombinant Proteins Cell biology Clone Cells Metabolic pathway 030104 developmental biology HEK293 Cells Biochemistry and Cell Biology Metabolic Networks and Pathways |
| Zdroj: | Cell systems, vol 3, iss 5 Cell Syst. Artículos CONICYT CONICYT Chile instacron:CONICYT |
| ISSN: | 2405-4712 |
| Popis: | Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in CHO and associated them with >1,700 genes in the Cricetulus griseus genome. The genome-scale metabolic model based on this reconstruction, iCHO1766, and cell-line-specific models for CHO-K1, CHO-S, and CHO-DG44 cells provide the biochemical basis of growth and recombinant protein production. The models accurately predict growth phenotypes and known auxotrophies in CHO cells. With the models, we quantify the protein synthesis capacity of CHO cells and demonstrate that common bioprocess treatments, such as histone deacetylase inhibitors, inefficiently increase product yield. However, our simulations show that the metabolic resources in CHO are more than three times more efficiently utilized for growth or recombinant protein synthesis following targeted efforts to engineer the CHO secretory pathway. This model will further accelerate CHO cell engineering and help optimize bioprocesses. |
| Databáze: | OpenAIRE |
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