ArticleCell systems2016
A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism.
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Article in Cell systems, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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89citing papers in PubMed
13.9field-weighted citation impact, top 1% of its field
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Who cites it
89 citing papers in PubMed, 265 citations in OpenAlex.
- Improving recombinant protein productivity in CHO cells via multi-omics data integration.Bioresources and bioprocessing · 2026Review
- Toward a 4D genome annotation of CHO cells for biomanufacturing.Trends in biotechnology · 2026Review
- A community reconstruction of Chinese hamster metabolism and structural systems biology elucidate metabolic rewiring in lactate-free CHO cells.Cell systems · 2026Article
- Selecting methods for draft GEM generation in multicellular eukaryotes: a comparative analysis.BMC bioinformatics · 2026Article
- Delineating the Transcriptional and Phenotypic Impact from Biotherapeutic Glycoengineering.bioRxiv : the preprint server for biology · 2026Article
- Systematic data-driven genome-scale metabolic model reduction for bioprocess modeling: CHO culture case study.NPJ systems biology and applications · 2026Article
- Transcriptome-driven constraint-based modelling reveals metabolic targets for ovarian cancer.Cancer & metabolism · 2026Article
- Exploring CHO cell stability during prolonged passaging via eXplainable AI driven flux balance analysis.NPJ systems biology and applications · 2026Article
- Advancing recombinant protein production in CHO cells through metabolic engineering.Frontiers in bioengineering and biotechnology · 2026Review
- A Hybrid Modeling Framework for Predictive Digital Twins of CHO Cell Culture.Computational and structural biotechnology journal · 2026Article
- Engineering mammalian protein secretion: Toward the convergence of high-throughput biology and computational methods.Cell systems · 2025Review
- Redefining media blending mathematically: a systematic approach for screening of medium components.Applied microbiology and biotechnology · 2025Article
- Integration of Bayesian optimization and solution thermodynamics to optimize media design for mammalian biomanufacturing.iScience · 2025Article
- Novel Data-Driven Mechanistic Modeling of Untargeted Metabolome Data Reveals Feed Component Effects in CHO Cell Bioprocess Using Column Generation-Based EFMs.Biotechnology journal · 2025Article
- Flux Sampling Suggests Metabolic Signatures of High Antibody-Producing CHO Cells.Biotechnology and bioengineering · 2025Article
- Defining Golden Batches in Biomanufacturing Processes From Internal Metabolic Activity to Detect Process Changes That May Affect Product Quality.Biotechnology and bioengineering · 2025Article
- Fantastic genes and where to find them expressed in CHO.Computational and structural biotechnology journal · 2025Article
- Wheels turning: CHO cell modeling moves into a digital biomanufacturing era: Subtitle: CHO Metabolic Modeling.Computational and structural biotechnology journal · 2025Review
- Unraveling productivity-enhancing genes in Chinese hamster ovary cells via CRISPR activation screening using recombinase-mediated cassette exchange system.Metabolic engineering · 2025Article
- Multi-scale design and optimization of antibody production via flexible nets.Computational and structural biotechnology journal · 2025Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
40 authors at 10 institutions in 10 countries.
Hooman HefziDepartment 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.
Kok Siong AngDepartment 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.
Michael HanschoDepartment of Biotechnology, University of Natural Resources and Life Sciences, Vienna, 1190 Vienna, Austria; Austrian Centre of Industrial Biotechnology, 1190 Vienna, Austria.
Aarash BordbarDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
David RuckerbauerDepartment of Biotechnology, University of Natural Resources and Life Sciences, Vienna, 1190 Vienna, Austria; Austrian Centre of Industrial Biotechnology, 1190 Vienna, Austria.
Meiyappan LakshmananBioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, 06-01, Centros, Singapore 138668, Singapore.
Camila A OrellanaAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Building 75), Brisbane, QLD 4072, Australia.
Deniz Baycin-HizalDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Yingxiang HuangBioinformatics and Systems Biology Program, University of California, San Diego, La Jolla 92093, CA, USA.
Daniel LeyDepartment 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.
Veronica S MartinezAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Building 75), Brisbane, QLD 4072, Australia.
Sarantos KyriakopoulosBioprocessing Technology Institute, Agency for Science, Technology and Research (A(∗)STAR), 20 Biopolis Way, 06-01, Centros, Singapore 138668, Singapore.
Natalia E JiménezCentre 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.
Daniel C ZielinskiDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Lake-Ee QuekAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Building 75), Brisbane, QLD 4072, Australia.
Tune WulffNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Johnny ArnsdorfNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Shangzhong LiDepartment 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.
Jae Seong LeeNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Giuseppe PagliaCenter for Systems Biology, University of Iceland, 101 Reykjavik, Iceland.
Nicolas LoiraCentre 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.
Philipp N SpahnDepartment 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.
Lasse E PedersenNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Jahir M GutierrezDepartment 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.
Zachary A KingDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Anne Mathilde LundDepartment 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.
Harish NagarajanBioinformatics and Systems Biology Program, University of California, San Diego, La Jolla 92093, CA, USA.
Alex ThomasNovo 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.
Alyaa M Abdel-HaleemNovo 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.
Juergen ZanghelliniDepartment of Biotechnology, University of Natural Resources and Life Sciences, Vienna, 1190 Vienna, Austria; Austrian Centre of Industrial Biotechnology, 1190 Vienna, Austria.
Helene F KildegaardNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Bjørn G VoldborgNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Ziomara P GerdtzenCentre 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.
Michael J BetenbaughDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Bernhard O PalssonDepartment 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 University of Denmark, 2800 Kgs. Lyngby, Denmark; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
Mikael R AndersenDepartment of Systems Biology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Lars K NielsenAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Building 75), Brisbane, QLD 4072, Australia.
Nicole BorthDepartment 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.
Dong-Yup LeeDepartment 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. Electronic address: cheld@nus.edu.sg.
Nathan E LewisNovo 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.
Novo Nordisk Foundation · DKFoundation Center · USUniversity of California San Diego · USAgency for Science, Technology and Research · SGAustrian Centre of Industrial Biotechnology (Austria) · ATThe University of Queensland · AUInstitute of Mathematics and Mathematical Modeling · KZJohns Hopkins University · USTechnical University of Denmark · DKUniversity of Iceland · IS
Funding
Unraveling the mammalian secretory pathway through systems biology and algorithm developmentR35GM119850 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEWIS, NATHAN ENOCH · 2016 to 2025
$4.3MNIGMS NIH HHS R35 GM119850
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.
Indexed as
GenomeAnimalsCHO CellsConsensusCricetinaeCricetulusHumansMetabolic Networks and PathwaysRecombinant ProteinsRecombinant Proteinsbiotherapeutic protein productionChinese hamster ovaryCHOgenome-scale modelmetabolic networksystems biology
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