Alves, Paula MarquesTeixeira, Ana Margarida PalmaDuarte, Tiago Martins da Costa2018-12-272019-05-3120162016-06http://hdl.handle.net/10362/55746Chinese hamster ovary (CHO) cells are preferred mammalian hosts for industrial production of therapeutic glycoproteins such as monoclonal antibodies (mAbs), used to treat cancer and immunological disorders. In these cells, the glutamine synthetase (GS) expression system has been widely used for efficient selection of high-yielding clones. However, fundamental knowledge on the metabolic behavior of GS-CHO cells in culture and its impact on product yields have not been yet systematized. The overall objective of this thesis was to comprehensively analyse the metabolome and fluxome of CHO cells exploring how the metabolism is affected by clonal variability and culture conditions. This information is then used to generate hypotheses on how metabolic wiring impacts mAb production.(...)engMetabolomicsFluxomicsdoctoral thesis