查看文章

In the last years, the Baculovirus Expression Vector System (BEVS) has gained increasing interest for its many biotechnologically relevant applications, ranging from single proteins to multi-subunit complexes such as virus like particles or adeno-associated viruses. The decrease in specific productivities that occurs when the cells are infected at high cell densities or “cell density effect” is a major drawback for these applications. In this work, a quantitative analysis of cell density related alterations of the central metabolism of insect cells has been performed. The most relevant metabolites, cofactors and central metabolism enzymes were profiled along cultures and Metabolic Flux Analysis was applied at different cell densities. Our results demonstrate the occurrence of major alterations on enzyme activities and fluxes at high cell densities, which have a profound impact on the energetic state of the cells and …