Fermentanomics: Monitoring Mammalian Cell Cultures with NMR Spectroscopy
Abstract
As the number of therapeutic proteins produced by mammalian cell cultures in the pharmaceutical industry continues to increase, the need to improve productivity and ensure consistent product quality during process development activities becomes more significant. Rational medium design is known to improve cell culture performance, but an understanding of nutrient consumption and metabolite accumulation within the medium is required. To this end, we have developed a technique for using 1D (1)H NMR to quantitate nonprotein feed components and metabolites in mammalian cell cultures. We refer to the methodology as "Fermentanomics" to differentiate it from standard metabolomics. The method was found to generate spectra with excellent water suppression, signal-to-noise, and resolution. More importantly, nutrient consumption and metabolite accumulation was readily observed. In total, 50 media components have been identified and quantitated. The application of Fermentanomics to the optimization of a proprietary CHO basal medium yielded valuable insight regarding the nutrient levels needed to maintain productivity. While the focus here is on the extracellular milieu of CHO cell cultures, this methodology is generally applicable to quantitating intracellular concentrations and can be extended to other mammalian cell lines, as well as platforms such as yeasts, fungi, and Escherichia coli.
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NMR systems have been employed for live-monitoring cancer cells and microorganisms cultures through flow NMR systems.
“To this end, NMR systems have been employed for quite some time in live-monitoring cancer cells and microorganisms cultures, through the introduction of cutting-edge flow NMR systems.148,149”
From Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products (2024) · cites this paper as [148]
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- Authors
- Bradley, S. A., Ouyang, A., Purdie, J., Smitka, T. A., Wang, T., & Kaerner, A.
- Affiliations
- Eli Lilly (United States) (US)
- Corresponding author
- Kaerner, Andreas
- ORCID
- Bradley, Scott A.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-06-25
- Volume
- 132
- Issue
- 28
- Pages
- 9531-9533
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2071412002
- Cited by
- 80
- References
- 12
- Citations by year
- 2024: 6 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 11 · 2014: 6 · 2013: 15 · 2012: 7
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
- Keywords
- nutrient consumption, metabolite accumulation, CHO cell culture, therapeutic protein production, process development, water suppression
- MeSH terms
- Animals, Cricetulus, Culture Media, Cricetinae, Magnetic Resonance Spectroscopy, CHO Cells
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