ArticleBioprocess and biosystems engineering2011
Quantitative characterization of metabolism and metabolic shifts during growth of the new human cell line AGE1.HN using time resolved metabolic flux analysis.
Article in Bioprocess and biosystems engineering, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed.
- Improved flux profiling in genome-scale modeling of human cell metabolism.Cell reports methods · 2026Article
- A Comprehensive Model for Separating Systematic Bias and Noise in Metabolomic Timecourse Data-A Nonlinear B-Spline Mixed-Effects Approach.Biotechnology and bioengineering · 2025Article
- Kinetic modelling of the cellular metabolic responses underpinning in vitro glycolysis assays.FEBS open bio · 2024Article
- Sodium acetate increases the productivity of HEK293 cells expressing the ECD-Her1 protein in batch cultures: experimental results and metabolic flux analysis.Frontiers in bioengineering and biotechnology · 2024Article
- Brain microvascular endothelial cell metabolism and its ties to barrier function.Vitamins and hormones · 2024Article
- Dark accumulation of downstream glycolytic intermediates initiates robust photosynthesis in cyanobacteria.Plant physiology · 2023Article
- Isotope-Assisted Metabolic Flux Analysis: A Powerful Technique to Gain New Insights into the Human Metabolome in Health and Disease.Metabolites · 2022Review
- Metabolomic and kinetic investigations on the electricity-aided production of butanol byEngineering in life sciences · 2021Article
- The shortcomings of accurate rate estimations in cultivation processes and a solution for precise and robust process modeling.Bioprocess and biosystems engineering · 2020Article
- The role of magnetic field in the biopharmaceutical production: Current perspectives.Biotechnology reports (Amsterdam, Netherlands) · 2019Review
- Oxygen Uptake Rate Soft-Sensing via DynamicFrontiers in bioengineering and biotechnology · 2019Article
- An unconventional uptake rate objective function approach enhances applicability of genome-scale models for mammalian cells.NPJ systems biology and applications · 2019Article
- Metabolic characterization of a CHO cell size increase phase in fed-batch cultures.Applied microbiology and biotechnology · 2017Article
- Estimation of time-varying growth, uptake and excretion rates from dynamic metabolomics data.Bioinformatics (Oxford, England) · 2017Article
- Segmented linear modeling of CHO fed-batch culture and its application to large scale production.Biotechnology and bioengineering · 2017Article
- Identifying model error in metabolic flux analysis - a generalized least squares approach.BMC systems biology · 2016Article
- Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism.Metabolic engineering communications · 2015Article
- A correction method for systematic error in (1)H-NMR time-course data validated through stochastic cell culture simulation.BMC systems biology · 2015Article
- Macroscopic modeling of mammalian cell growth and metabolism.Applied microbiology and biotechnology · 2015Review
- Methods and advances in metabolic flux analysis: a mini-review.Journal of industrial microbiology & biotechnology · 2015Review
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5 authors.
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Abstract
For the improved production of vaccines and therapeutic proteins, a detailed understanding of the metabolic dynamics during batch or fed-batch production is requested. To study the new human cell line AGE1.HN, a flexible metabolic flux analysis method was developed that is considering dynamic changes in growth and metabolism during cultivation. This method comprises analysis of formation of cellular components as well as conversion of major substrates and products, spline fitting of dynamic data and flux estimation using metabolite balancing. During batch cultivation of AGE1.HN three distinct phases were observed, an initial one with consumption of pyruvate and high glycolytic activity, a second characterized by a highly efficient metabolism with very little energy spilling waste production and a third with glutamine limitation and decreasing viability. Main events triggering changes in cellular metabolism were depletion of pyruvate and glutamine. Potential targets for the improvement identified from the analysis are (i) reduction of overflow metabolism in the beginning of cultivation, e.g. accomplished by reduction of pyruvate content in the medium and (ii) prolongation of phase 2 with its highly efficient energy metabolism applying e.g. specific feeding strategies. The method presented allows fast and reliable metabolic flux analysis during the development of producer cells and production processes from microtiter plate to large scale reactors with moderate analytical and computational effort. It seems well suited to guide media optimization and genetic engineering of producing cell lines.
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