PRODUCTION ORGANISMS AND EXPRESSION SYSTEMSDesign and development of all microbial production processes start with the selection of appropriate organisms, strains, and expression systems enabling high yields and high quality of a desired product with defi ned pharmacological properties. Industrially Established Recombinant Expression SystemsIndustrially established expressions systems for production of the marketed compounds are, besides inclusion, body-forming Escherichia coli strains, the yeast Saccharomyces cerevisiae and mammalian cells like CHO-and BHK-cells (Table 1.1-1). These systems were the genetically and physiologically most advanced and therefore mostly applied when recombinant production processes were starting to be developed in the mid-1980s and are now widely accepted by regulatory bodies. E. coli and S. cerevisiae can be grown cheaply and rapidly, are amenable to high cell density fermentations with biomasses of up to 130 g/L, possess short generation times, have high capacities to accumulate foreign proteins, are easy to handle, and are established fermentation organisms.However, because gene recombinant pharmaceuticals continuously gain an increasing importance in medicine and are expected to help curing diseases that are not yet treatable today, new expression systems have to be exploited enabling the production of such pharmaceuticals with innovative properties that simultaneously meet key criteria like consistent product quality and cost effectiveness. Of particular interest in this regard are expression systems enabling the secretion of TABLE 1.1-1. Industrially Used Recombinant Expression Systems