Characterizing steady states of genome-scale metabolic networks in continuous cell cultures.

ABSTRACT: In the continuous mode of cell culture, a constant flow carrying fresh media replaces culture fluid, cells, nutrients and secreted metabolites. Here we present a model for continuous cell culture coupling intra-cellular metabolism to extracellular variables describing the state of the bioreactor, taking into account the growth capacity of the cell and the impact of toxic byproduct accumulation. We provide a method to determine the steady states of this system that is tractable for metabolic networks of arbitrary complexity. We demonstrate our approach in a toy model first, and then in a genome-scale metabolic network of the Chinese hamster ovary cell line, obtaining results that are in qualitative agreement with experimental observations. We derive a number of consequences from the model t

SUBMITTER: Fernandez-de-Cossio-Diaz J 

PROVIDER: S-EPMC5703580 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature