A Top-Down Systems Biology Approach for the Identification of Targets for Fungal Strain and Process Development

Abstract

This chapter discusses approaches to select targets for improvement of production processes, with a special focus on the application of functional genomics technologies as an unbiased approach towards target selection. The development of a fungal production process starts with the selection of a strain that produces the compound of interest or with the construction of such a strain. Often only the obvious targets for metabolic engineering are addressed. In this chapter such a systems biology approach, based on the information gathered with functional genomics technologies and in combination with multivariate data analysis tools, is discussed as a method to achieve unbiased selection and ranking of targets for both strain improvement and bioprocess optimization. Besides classical approaches for strain development, such as screening for protease mutants and targeted disruption of known protease genes, a top-down systems biology approach was applied to further elucidate the proteolytic system and its regulation in A. niger. The ultimate goal is to identify new targets for further improvement of the fungal cell factory for heterologous protein production. The available selection methods for relevant targets for fungal strain and process development, or for that matter any microbial production process, have been very successful in numerous cases. Recently introduced functional genomics technologies in combination with multivariate data analysis (MVDA) tools enable an open and comprehensive top-down systems biology approach towards target selection. Due to its unbiased nature, a successful top-down systems biology approach will provide a new boost in the ongoing cycle of bioprocess optimization.