Cellular responses to protein production in the filamentous fungus Trichoderma reesei

The filamentous fungus Trichoderma reesei is known as an efficient producer of a variety of cellulases and hemicellulases, and it is used as an industrial host organism for production of the fungal enzymes as well as for heterologous proteins. Production of secreted proteins in large quantities, or production of heterologous proteins originating from distantly related organisms, are known to provoke stress responses in the cells. The known stress responses include e.g. activation of the unfolded protein response (UPR) pathway resulting in induction of a number of genes needed in enhancement of protein folding and transport. The fungal cells have also a feed-back mechanism to reduce the load in the secretory pathway by negative transcriptional regulation of genes encoding the major secreted proteins.

The availability of the genome sequence information has made it possible to apply genome-wide approaches in studies of the cellular responses to protein production under different conditions and to obtain further information on protein production and factors influencing it at different physiological conditions. We have applied transcriptome and proteome analysis to study the effects of production of heterologous proteins in T. reesei, as well as to analyse different protein production conditions in batch bioreactor and chemostat cultures. Specifically, we have analysed protein production and cellular responses in carbon-limited chemostat cultures at different specific growth rates and cell densities.