Metabolite profiling of CHO cells with different growth characteristics

作者：Stefanie Dietmair, Mark P. Hodson, Lake‐Ee Quek, Nicholas E. Timmins, Panagiotis K. Chrysanthopoulos, Shana Sunny Jacob, Peter P. Gray, Lars Keld Nielsen · 发表于：Biotechnology and Bioengineering · 年份：2012 · DOI：10.1002/bit.24496 · 被引用次数：115 · 研究领域：Viral Infectious Diseases and Gene Expression in Insects、Protein purification and stability、Microbial Metabolic Engineering and Bioproduction

Mammalian cell cultures are the predominant system for the production of recombinant proteins requiring post-translational modifications. As protein yields are a function of growth performance (among others), and performance varies greatly between culture medium (e.g., different growth rates and peak cell densities), an understanding of the biological mechanisms underpinning this variability would facilitate rational medium and process optimization, increasing product yields, and reducing costs. We employed a metabolomics approach to analyze differences in metabolite concentrations of CHO cells cultivated in three different media exhibiting different growth rates and maximum viable cell densities. Analysis of intra- and extracellular metabolite concentrations over the course of the cultures using a combination of HPLC and GC-MS, readily detected medium specific and time dependent changes. Using multivariate data analysis, we identified a range of metabolites correlating with growth rate, illustrating how metabolomics can be used to relate gross phenotypic changes to the fine details of cellular metabolism.