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A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism.
Hefzi, Hooman; Ang, Kok Siong; Hanscho, Michael; Bordbar, Aarash; Ruckerbauer, David; Lakshmanan, Meiyappan; Orellana, Camila A; Baycin-Hizal, Deniz; Huang, Yingxiang; Ley, Daniel; Martinez, Veronica S; Kyriakopoulos, Sarantos; Jiménez, Natalia E; Zielinski, Daniel C; Quek, Lake-Ee; Wulff, Tune; Arnsdorf, Johnny; Li, Shangzhong; Lee, Jae Seong; Paglia, Giuseppe; Loira, Nicolas; Spahn, Philipp N; Pedersen, Lasse E; Gutierrez, Jahir M; King, Zachary A; Lund, Anne Mathilde; Nagarajan, Harish; Thomas, Alex; Abdel-Haleem, Alyaa M; Zanghellini, Juergen; Kildegaard, Helene F; Voldborg, Bjørn G; Gerdtzen, Ziomara P; Betenbaugh, Michael J; Palsson, Bernhard O; Andersen, Mikael R; Nielsen, Lars K; Borth, Nicole; Lee, Dong-Yup; Lewis, Nathan E.
Afiliación
  • Hefzi H; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability at the School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ang KS; Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, 06-01, Centros, Singapore 138668, Singapore.
  • Hanscho M; Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, 1190 Vienna, Austria; Austrian Centre of Industrial Biotechnology, 1190 Vienna, Austria.
  • Bordbar A; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ruckerbauer D; Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, 1190 Vienna, Austria; Austrian Centre of Industrial Biotechnology, 1190 Vienna, Austria.
  • Lakshmanan M; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, 06-01, Centros, Singapore 138668, Singapore.
  • Orellana CA; Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Building 75), Brisbane, QLD 4072, Australia.
  • Baycin-Hizal D; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Huang Y; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla 92093, CA, USA.
  • Ley D; Department of Systems Biology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
  • Martinez VS; Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Building 75), Brisbane, QLD 4072, Australia.
  • Kyriakopoulos S; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, 06-01, Centros, Singapore 138668, Singapore.
  • Jiménez NE; Centre for Biotechnology and Bioengineering, Department of Chemical Engineering and Biotechnology, University of Chile, Santiago 8370456, Chile; MATHomics, Center for Mathematical Modeling; Center for Genome Regulation (Fondap 15090007), University of Chile, Santiago 8370456, Chile.
  • Zielinski DC; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Quek LE; Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Building 75), Brisbane, QLD 4072, Australia.
  • Wulff T; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
  • Arnsdorf J; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
  • Li S; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability at the School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Lee JS; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
  • Paglia G; Center for Systems Biology, University of Iceland, 101 Reykjavik, Iceland.
  • Loira N; Centre for Biotechnology and Bioengineering, Department of Chemical Engineering and Biotechnology, University of Chile, Santiago 8370456, Chile; MATHomics, Center for Mathematical Modeling; Center for Genome Regulation (Fondap 15090007), University of Chile, Santiago 8370456, Chile.
  • Spahn PN; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability at the School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Pedersen LE; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
  • Gutierrez JM; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability at the School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • King ZA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Lund AM; Department of Systems Biology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
  • Nagarajan H; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla 92093, CA, USA.
  • Thomas A; Novo Nordisk Foundation Center for Biosustainability at the School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla 92093, CA, USA.
  • Abdel-Haleem AM; Novo Nordisk Foundation Center for Biosustainability at the School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Computational Bioscience Research Centre, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
  • Zanghellini J; Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, 1190 Vienna, Austria; Austrian Centre of Industrial Biotechnology, 1190 Vienna, Austria.
  • Kildegaard HF; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
  • Voldborg BG; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
  • Gerdtzen ZP; Centre for Biotechnology and Bioengineering, Department of Chemical Engineering and Biotechnology, University of Chile, Santiago 8370456, Chile; MATHomics, Center for Mathematical Modeling; Center for Genome Regulation (Fondap 15090007), University of Chile, Santiago 8370456, Chile.
  • Betenbaugh MJ; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Palsson BO; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability at the School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability, Technical Un
  • Andersen MR; Department of Systems Biology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
  • Nielsen LK; Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Building 75), Brisbane, QLD 4072, Australia.
  • Borth N; Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, 1190 Vienna, Austria; Austrian Centre of Industrial Biotechnology, 1190 Vienna, Austria. Electronic address: nicole.borth@boku.ac.at.
  • Lee DY; Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore; Bioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, 06-01, Centros, Singapore 138668, Singapore. E
  • Lewis NE; Novo Nordisk Foundation Center for Biosustainability at the School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: nlewisres@ucsd.edu.
Cell Syst ; 3(5): 434-443.e8, 2016 11 23.
Article en En | MEDLINE | ID: mdl-27883890
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Genoma Tipo de estudio: Guideline / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Syst Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Genoma Tipo de estudio: Guideline / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Syst Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos