A functional genomics study of extracellular protease production by Aspergillus niger

Braaksma, M. (2010)

Doctoral Thesis

The objective of the project described in this thesis was to study the complex induction of extracellular proteases in the filamentous fungus Aspergillus niger using information gathered with functional genomics technologies. A special emphasis is given to the requirements for performing a successful systems biology study and addressing the challenges met in analyzing the large, information-rich data sets generated with functional genomics technologies. The role that protease activity plays in strain and process development of A. niger and other aspergilli is reviewed. The influence of several environmental factors on the production of extracellular proteases of A. niger in controlled batch cultivations was studied. Samples generated in this study were used for analysis with different functional genomics technologies. With a shotgun proteomics approach the A. niger secretome under different experimental conditions was determined. Furthermore, the effect of different quantitative phenotypes related to protease or glucoamylase activity on the information content of a metabolomics data set was investigated. Finally, the clustering of co-expressed genes is described. First, a set of conserved genes was used to construct gene co-expression networks. Subsequently, all protein-coding A. niger genes, including hypothetical and poorly conserved genes, were integrated into the co-expression analysis.

• Proteomics
• Metabolomics
• Transcriptomics
• Gene co-expression network
• Systems biology
• Functional genomics
• Production optimization
• Experimental design

• All authors: Braaksma, M.
• Supervisor: Punt, P.J.; Hondel, C.A.M.J.J. van den
• Co-supervisor: Werf, M.J. van der
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Science, Leiden University
• Date: 2010-12-15