Correlation of gene expression and protein production rate: A system wide study

The filamentous fungi Trichoderma reesei is an industrial protein production host with exceptional protein secretion capability. It can produce up 100 g/l of protein and it is often used to produce cellulases and hemicellulases to depolymerise biomass. Most efficient production of secreted protein is achieved at low specific growth rate of 0.03 1/h (Pakula et al. Microbiology 151 (2005), 135-143). We have used transcriptomics and proteomics to study the effect of growth rate and cell density to T. reesei protein production in chemostat cultivations. Use of chemostat allows control of growth rate and precise estimation of the specific protein production rate (SPPR). For each gene we calculate its correlation to the SPPR and analyse the distribution of these correlations in context of genome structure and annotation, gene sequence homology to other fungi and predicted metabolic network. Although highest protein production occurs at low growth rate and carbon limitation the observed response is distinct from Saccharomyces cerevisiae's response to low growth rate or carbon limitation. In addition to conventional transcriptomics by microarray, the used microarray also included probes for non-coding sequence to detect novel genes (Arvas et al. Gene 467 (2010) 41-51). Several novel genes, putatively related to regulation, were discovered as differentially expressed in these conditions.