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Open Access Highly Accessed Research article

Correlation of gene expression and protein production rate - a system wide study

Mikko Arvas1*, Tiina Pakula1, Bart Smit2, Jari Rautio3, Heini Koivistoinen4, Paula Jouhten1, Erno Lindfors1, Marilyn Wiebe1, Merja Penttilä1 and Markku Saloheimo1

Author Affiliations

1 VTT Technical Research Centre of Finland, Tietotie 2, P.O. Box FI-1000, 02044 VTT, Espoo, Finland

2 NIZO food research, Kernhemseweg 2, 6718ZB Ede, the Netherlands

3 Plexpress, Viikinkaari 6, 00790 Helsinki, Finland

4 Ypap Oy, Hyrsynkulmantie 68, FI-32100 Ypäjä, Finland

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BMC Genomics 2011, 12:616  doi:10.1186/1471-2164-12-616

Published: 20 December 2011

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 the first analysis on genome wide effects of growth rate. In this work we study the filamentous fungus Trichoderma reesei (Hypocrea jecorina) that is an industrial protein production host known for its exceptional protein secretion capability. Interestingly, it exhibits a low 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 chemostat cultivations of T. reesei. Use of chemostat allowed control of growth rate and exact estimation of the extracellular specific protein production rate (SPPR). We find that major biosynthetic activities are all negatively correlated with SPPR. We also find that expression of many genes of secreted proteins and secondary metabolism, as well as various lineage 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 protein production. Also, we propose that flux through early glycolysis or the TCA cycle is a more fundamental determining factor than growth rate for low growth rate protein production and we propose a novel eukaryotic response to this i.e. the lineage specific response (LSR).