ArticleMetabolites2021
A Metabolomics Approach to Increasing Chinese Hamster Ovary (CHO) Cell Productivity.
Article in Metabolites, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Metabolic Flux Analysis Reveals Cell Line-Specific Rewiring in CHO Cells Following TCA Cycle Intermediate Feeding for Bioprocess pH Control.Biotechnology and bioengineering · 2026Article
- Data-Driven Approach for Bioreactor Monitoring and Prediction in Monoclonal Antibody Production.ACS omega · 2026Article
- Improving recombinant protein productivity in CHO cells via multi-omics data integration.Bioresources and bioprocessing · 2026Review
- Effect of Fermentation Time and Heat Treatment on Yield and In Vitro Antioxidant and Antimicrobial Activity of Postbiotics from Mixed Bifidobacterium and Lactobacillus Co-Fermentations.Current microbiology · 2026Article
- Challenges and solutions for upstream processing of complex biologics.Antibody therapeutics · 2026Review
- Thrombomodulin is essential for recombinant Fc-fusion protein production in Chinese hamster ovary cells via multiple signaling pathways.Journal of biological engineering · 2025Article
- Temporal Galactose-Manganese Feeding in Fed-Batch and Perfusion Bioreactors Modulates UDP-Galactose Pools for Enhanced mAb Glycosylation Homogeneity.Biotechnology and bioengineering · 2025Article
- Time-Resolved Hierarchical Modeling Highlights Metabolites Influencing Productivity and Cell Death in Chinese Hamster Ovary Cells.Biotechnology journal · 2025Article
- Identification of cellular signatures associated with chinese hamster ovary cell adaptation for secretion of antibodies.Computational and structural biotechnology journal · 2025Article
- Exploring metabolic effects of dipeptide feed media on CHO cell cultures by in silico model-guided flux analysis.Applied microbiology and biotechnology · 2024Article
- Advancements in CHO metabolomics: techniques, current state and evolving methodologies.Frontiers in bioengineering and biotechnology · 2024Review
- From observational to actionable: rethinking omics in biologics production.Trends in biotechnology · 2023Review
- Enhancing productivity of Chinese hamster ovary (CHO) cells: synergistic strategies combining low-temperature culture and mTORC1 signaling engineering.Frontiers in bioengineering and biotechnology · 2023Article
- Strategies and Considerations for Improving Recombinant Antibody Production and Quality in Chinese Hamster Ovary Cells.Frontiers in bioengineering and biotechnology · 2022Review
- Protein hydrolysates in cell culture: Toward multi-omics characterization.Biotechnology progressReview
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Much progress has been made in improving the viable cell density of bioreactor cultures in monoclonal antibody production from Chinese hamster ovary (CHO) cells; however, specific productivity (qP) has not been increased to the same degree. In this work, we analyzed a library of 24 antibody-expressing CHO cell clones to identify metabolites that positively associate with qP and could be used for clone selection or medium supplementation. An initial library of 12 clones, each producing one of two antibodies, was analyzed using untargeted LC-MS experiments. Metabolic model-based annotation followed by correlation analysis detected 73 metabolites that significantly correlated with growth, qP, or both. Of these, metabolites in the alanine, aspartate, and glutamate metabolism pathway, and the TCA cycle showed the strongest association with qP. To evaluate whether these metabolites could be used as indicators to identify clones with potential for high productivity, we performed targeted LC-MS experiments on a second library of 12 clones expressing a third antibody. These experiments found that aspartate and cystine were positively correlated with qP, confirming the results from untargeted analysis. To investigate whether qP correlated metabolites reflected endogenous metabolic activity beneficial for productivity, several of these metabolites were tested as medium additives during cell culture. Medium supplementation with citrate improved qP by up to 490% and more than doubled the titer. Together, these studies demonstrate the potential for using metabolomics to discover novel metabolite additives that yield higher volumetric productivity in biologics production processes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.