Project name: Trichoderma reesei

Description: Comparison of T. reesei grown on lactose fed chemostat cultivations in different growth rates and cell densitiesThe analysis is further described in paper Correlation of gene expression and protein production rate - a system wide study. Mikko Arvas, Tiina Pakula, Bart Smit, Jari Rautio, Heini Koivistoinen, Paula Jouhten, Erno Lindfors, Marilyn Wiebe, Merja Penttilä and Markku Saloheimo, Submitted.Abstract:Background:Growth rate is a major determinant of intracellular function. However its effects can only be properly dissected with technically demanding chemostat cultivations in which it can be controlled. Recent work on Saccharomyces cerevisiae chemostat cultivations provided thefirst analysis on genome wide effects of growth rate. In this work westudy the filamentous fungus Trichoderma reesei (Hypocreajecorina) that is an industrial protein production host known for itsexceptional protein secretion capability. Interestingly, it exhibits alow growth rate protein production phenotype.Results: We have used transcriptomics and proteomics to study the effect of growth rate and cell density on protein production in chemostatcultivations of T. reesei. Use of chemostat allowed control ofgrowth rate and exact estimation of the extracellular specific proteinproduction rate (SPPR). We find that major biosynthetic activities areall negatively correlated with SPPR. We also find that expression ofmany genes of secreted proteins and secondary metabolism, as well as variouslineage specific, mostly unknown genes are positively correlated with SPPR.Finally, we enumerate possible regulators and regulatory mechanisms,arising from the data, for this response.Conclusions: Based on these results it appears that in low growth rate protein production energy is very efficiently used primarly for proteinproduction. Also, we propose that flux through early glycolysis orthe TCA cycle is a more fundamental determining factor than growth ratefor low growth rate protein production and we propose a noveleukaryotic response to this i.e. the lineage specific response (LSR).Overall design: A nine chip study using total RNA recovered from three separate cultures of T. reesei RutC-30 grown with growth rate 0.03, three separate cultures grown with growth rate 0.06 and three separate cultures grown with growth rate 0.03 in high cell density.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Other

Last updated: 2011-07-06