A Combinatorial Mutagenesis Approach to Improve Microbial Expression Systems

Proteins have a broad range of medical and industrial applications, and today the majority of all commercial proteins are produced recombinantly, most often by using bacteria and yeast as production hosts. The scientific literature on microbial recombinan t protein production is comprehensive, but it is still difficult to predict how production processes (genetic tools, choice of production host, cultivation conditions) shall be designed in order to achieve effective production of any given protein. This h olds for both bacteria and yeast, and accordingly each new protein must typically be tested in a trail-and-error approach, which is both time consuming and cost-inefficient. We believe that this may partly be explained by the fact that few research groups have a focus on integrating basic molecular biology insights and process development. In this project we wish to focus on this type of integrated research both to develop improved expression systems as well as to generate new insights into so far poorly understood genetic and physiological parameters that play important roles in determining protein expression and secretion efficiently. This project will contribute to generation of new key competence with high value to all Norwegian industry working with different aspects of recombinant protein production.