title: Metabolic flux rewiring in mammalian cell cultures.
abstract: Continuous cell lines (CCLs) engage in 'wasteful' glucose and glutamine metabolism that leads to accumulation of inhibitory byproducts, primarily lactate and ammonium. Advances in techniques for mapping intracellular carbon fluxes and profiling global changes in enzyme expression have led to a deeper understanding of the molecular drivers underlying these metabolic alterations. However, recent studies have revealed that CCLs are not necessarily entrenched in a glycolytic or glutaminolytic phenotype, but instead can shift their metabolism toward increased oxidative metabolism as nutrients become depleted and/or growth rate slows. Progress to understand dynamic flux regulation in CCLs has enabled the development of novel strategies to force cultures into desirable metabolic phenotypes, by combining fed-batch feeding strategies with direct metabolic engineering of host cells.
authors.affiliation: Department of Chemical and Biomolecular Engineering, PMB 351604, Vanderbilt University, Nashville, TN 37235-1604, USA; Department of Molecular Physiology and Biophysics, PMB 351604, Vanderbilt University, Nashville, TN 37235-1604, USA. Electronic address: j.d.young@vanderbilt.edu.
authors.forename: Jamey D
authors.initials: JD
authors.lastname: Young
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002477:Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D060847:Metabolic Engineering; D064688:Metabolic Flux Analysis; D010085:Oxidative Phosphorylation
chemical_list: D005973:Glutamine; D019344:Lactic Acid; D005947:Glucose