Abstract
The biopharmaceuticals market is currently outperforming the pharmaceuticals market and is now valued at US$ 48 billion with an average annual growth of 19%. Behind this success is a 100-fold increase in productivities of eukaryotic expression systems. However, the productivity per cell has remained unchanged for more than 10 years. The engineering of the ER-resident protein folding machinery is discussed together with an overview of signal transduction pathways activated by heterologous protein overexpression to increase cell specific productivities.