A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism.

TitleA Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism.
Publication TypeJournal Article
Year of Publication2016
AuthorsHefzi H, Ang KSiong, Hanscho M, Bordbar A, Ruckerbauer D, Lakshmanan M, Orellana CA, Baycin-Hizal D, Huang Y, Ley D, Martinez VS, Kyriakopoulos S, Jiménez NE, Zielinski DC, Quek L-E, Wulff T, Arnsdorf J, Li S, Lee JSeong, Paglia G, Loira N, Spahn PN, Pedersen LE, Gutierrez JM, King ZA, Lund AMathilde, Nagarajan H, Thomas A, Abdel-Haleem AM, Zanghellini J, Kildegaard HF, Voldborg BG, Gerdtzen ZP, Betenbaugh MJ, Palsson BO, Andersen MR, Nielsen LK, Borth N, Lee D-Y, Lewis NE
JournalCell Syst
Volume3
Issue5
Pagination434-443.e8
PubMed Date11/2016
ISSN2405-4712
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.

Alternate JournalCell Syst
PubMed ID27883890
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