EUROCORES_EUROSCOPE 1. Call_Genome-Wide Comparison of Physiological Bottlenecks in Multi-Subunit Protein Production in Prokaryotic and Eukaryotic Microbial Hosts

Heterologous protein production has proven to be successful in many cases during the last two decades. However, the production of complex proteins has turned out to have a very low success rate. In the past, a lot of information on different molecular, biochemical and biological properties of different host cells has been obtained, but this information has been gained in a variety of noncomparable ways, providing very little information for generalisation. The general concept of this project is a comparative genome-wide analysis of different host species (with proven, different capacities for protein expression) for functional, structural and regulatory processes involved in expression of complex proteins. In addition, efficiency of secretion, folding and solubility shall be compared in different host systems at different critical environmental conditions (pH, temperature, osmolarity and oxidative stress) and analysed on the transcriptomic and proteomic level with the aim to identify main bottlenecks or major pacemakers of efficient protein production. Thorough data analysis will enable both the identification of common patterns of cellular reactions to expression of complex proteins, and of specific features of certain expression systems. This novel approach will guide new approaches to engineer expression systems for superior abilities to express complex proteins.