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Systematically gap-filling the genome-scale metabolic model of CHO cells

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Abstract

Objective

Chinese hamster ovary (CHO) cells are the leading cell factories for producing recombinant proteins in the biopharmaceutical industry. In this regard, constraint-based metabolic models are useful platforms to perform computational analysis of cell metabolism. These models need to be regularly updated in order to include the latest biochemical data of the cells, and to increase their predictive power. Here, we provide an update to iCHO1766, the metabolic model of CHO cells.

Results

We expanded the existing model of Chinese hamster metabolism with the help of four gap-filling approaches, leading to the addition of 773 new reactions and 335 new genes. We incorporated these into an updated genome-scale metabolic network model of CHO cells, named iCHO2101. In this updated model, the number of reactions and pathways capable of carrying flux is substantially increased.

Conclusions

The present CHO model is an important step towards more complete metabolic models of CHO cells.

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Acknowledgements

This work was facilitated through generous funding from the Novo Nordisk Foundation through Center for Biosustainability at the Technical University of Denmark (NNF10CC1016517).

Supplementary Informatio

Supplementary Table 1—The distribution of blocked reactions of iCHO1766 in all metabolic pathways.

Supplementary Table 2—The list of new reactions added by using GapFill method.

Supplementary Table 3—The list of new reactions added by using GAUGE method.

Supplementary Table 4—The list of metabolites that were labeled as “detected in human biofluids” in HMDB and the new reactions associated with them.

Supplementary Table 5—The list of metabolites that were labeled as “expected to be detected in human biofluids” in HMDB and the new reactions associated with them.

Supplementary Table 6—The list of blocked repetitive reactions in iCHO1766 that have been suggested for deletion.

Supplementary Table 7—The list of new transport reactions that have a similar reaction in a subcellular part with no genes in iCHO1766.

Supplementary Table 8—The list of new reactions added by searching the BiGG database.

Supplementary Table 9—The list of the reactions in metabolic pathways and expression levels associated with them, both in iCHO1766 and iCHO2101.

Supplementary Table 10—The spreadsheet format of iCHO2101.

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Authors and Affiliations

  1. Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran

    Hamideh Fouladiha & Sayed-Amir Marashi

  2. Department of Bioengineering, University of California, San Diego, USA

    Shangzhong Li, Helen O. Masson & Nathan E. Lewis

  3. Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego, USA

    Shangzhong Li, Zerong Li, Helen O. Masson & Nathan E. Lewis

  4. Department of Pediatrics, University of California, San Diego, USA

    Zerong Li & Nathan E. Lewis

  5. Protein Chemistry and Proteomics Laboratory, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

    Behrouz Vaziri

  6. Department of Biotechnology, University of Tehran, Enghelab Avenue, 1417614411, Tehran, Iran

    Sayed-Amir Marashi

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  1. Hamideh Fouladiha
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Correspondence to Sayed-Amir Marashi.

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10529_2020_3021_MOESM1_ESM.xlsx

Electronic supplementary material 1 Supplementary Table 1: The distribution of blocked reactions of iCHO1766 in all metabolic pathways. Supplementary Table 2: The list of new reactions added by using GapFill method. Supplementary Table 3: The list of new reactions added by using GAUGE method. Supplementary Table 4: The list of metabolites that were labeled as “detected in human biofluids” in HMDB and the new reactions associated with them. Supplementary Table 5: The list of metabolites that were labeled as “expected to be detected in human biofluids” in HMDB and the new reactions associated with them. Supplementary Table 6: The list of blocked repetitive reactions in iCHO1766 that have been suggested for deletion. Supplementary Table 7: The list of new transport reactions that have a similar reaction in a subcellular part with no genes in iCHO1766. Supplementary Table 8: The list of new reactions added by searching the BiGG database. Supplementary Table 9: The list of the reactions in metabolic pathways and expression levels associated with them, both in iCHO1766 and iCHO2101. Supplementary Table 10: The spreadsheet format of iCHO2101. (XLSX 655 kb)

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Fouladiha, H., Marashi, SA., Li, S. et al. Systematically gap-filling the genome-scale metabolic model of CHO cells. Biotechnol Lett 43, 73–87 (2021). https://doi.org/10.1007/s10529-020-03021-w

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  • DOI: https://doi.org/10.1007/s10529-020-03021-w

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