Combined in silico modeling and metabolomics analysis to characterize fed‐batch CHO cell culture

• DOI: 10.1002/bit.24445
• Publication Date: 2012-01-17T18:09:53Z
• Authors: Suresh Selvarasu; Ying Swan Ho; William P. K. Chong; Niki S. C. Wong; Faraaz N. K. Yusufi; Yih Yean Lee; Miranda G. S. Yap; Dong‐Yup Lee
• Keywords: Metabolic pathway

Abstract The increasing demand for recombinant therapeutic proteins highlights the need to constantly improve efficiency and yield of these biopharmaceutical products from mammalian cells, which is fully achievable only through proper understanding cellular functioning. Towards this end, current study exploited a combined metabolomics in silico modeling approach gain deeper insight into mechanisms Chinese hamster ovary (CHO) fed‐batch cultures. Initially, extracellular intracellular metabolite profiling analysis shortlisted key metabolites associated with cell growth limitation within energy, glutathione, glycerophospholipid pathways that have distinct changes at exponential‐stationary transition phase In addition, biomass compositional newly revealed different amino acid content CHO cells other indicating significance accurate protein composition data balancing across required nutrient assimilation, metabolic utilization, growth. Subsequent characterized internal behaviors attaining physiological during non‐growth phases, thereby allowing us explore relevant identify major growth‐limiting factors including oxidative stress depletion lipid metabolites. Such information on growth‐related derived can potentially guide development new strategies enhance culture performance. Biotechnol. Bioeng. 2012; 109:1415–1429. © 2012 Wiley Periodicals, Inc.