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

Mikko Arvas, Tiina Pakula (Corresponding author), Bart Smit, Jari Rautio, Heini Koivistoinen, Paula Jouhten, Erno Lindfors, Marilyn Wiebe, Merja Penttilä, Markku Saloheimo

Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsScientific

Abstract

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. 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. 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).
Original languageEnglish
Title of host publicationAbstracts from the 11th European Conference on Fungal Genetics
PublisherNew Prairie Press
Pages244
DOIs
Publication statusPublished - 2012
Event11th European Conference on Fungal Genetics - Marburg, Germany
Duration: 30 Mar 20122 Apr 2012

Publication series

SeriesFungal Genetics Reports
Number6
Volume59
ISSN1941-4757

Conference

Conference11th European Conference on Fungal Genetics
CountryGermany
CityMarburg
Period30/03/122/04/12

Fingerprint

gene expression
proteins
Trichoderma reesei
protein secretion
glycolysis
transcriptomics
proteomics
growth factors
genes
phenotype
fungi
metabolism
genome
energy

Cite this

Arvas, M., Pakula, T., Smit, B., Rautio, J., Koivistoinen, H., Jouhten, P., ... Saloheimo, M. (2012). Correlation of gene expression and protein production rate: A system wide study. In Abstracts from the 11th European Conference on Fungal Genetics (pp. 244). [PR8.52] New Prairie Press. Fungal Genetics Reports, No. 6, Vol.. 59 https://doi.org/10.4148/1941-4765.1014
Arvas, Mikko ; Pakula, Tiina ; Smit, Bart ; Rautio, Jari ; Koivistoinen, Heini ; Jouhten, Paula ; Lindfors, Erno ; Wiebe, Marilyn ; Penttilä, Merja ; Saloheimo, Markku. / Correlation of gene expression and protein production rate : A system wide study. Abstracts from the 11th European Conference on Fungal Genetics. New Prairie Press, 2012. pp. 244 (Fungal Genetics Reports; No. 6, Vol. 59).
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Arvas, M, Pakula, T, Smit, B, Rautio, J, Koivistoinen, H, Jouhten, P, Lindfors, E, Wiebe, M, Penttilä, M & Saloheimo, M 2012, Correlation of gene expression and protein production rate: A system wide study. in Abstracts from the 11th European Conference on Fungal Genetics., PR8.52, New Prairie Press, Fungal Genetics Reports, no. 6, vol. 59, pp. 244, 11th European Conference on Fungal Genetics, Marburg, Germany, 30/03/12. https://doi.org/10.4148/1941-4765.1014

Correlation of gene expression and protein production rate : A system wide study. / Arvas, Mikko; Pakula, Tiina (Corresponding author); Smit, Bart; Rautio, Jari; Koivistoinen, Heini; Jouhten, Paula; Lindfors, Erno; Wiebe, Marilyn; Penttilä, Merja; Saloheimo, Markku.

Abstracts from the 11th European Conference on Fungal Genetics. New Prairie Press, 2012. p. 244 PR8.52 (Fungal Genetics Reports; No. 6, Vol. 59).

Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsScientific

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T1 - Correlation of gene expression and protein production rate

T2 - A system wide study

AU - Arvas, Mikko

AU - Pakula, Tiina

AU - Smit, Bart

AU - Rautio, Jari

AU - Koivistoinen, Heini

AU - Jouhten, Paula

AU - Lindfors, Erno

AU - Wiebe, Marilyn

AU - Penttilä, Merja

AU - Saloheimo, Markku

PY - 2012

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N2 - 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 Saccharomycescerevisiae 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 productionhost known for its exceptional protein secretion capability. Interestingly, it exhibits a low growth rate protein production phenotype. We have used transcriptomics and proteomics to study the effect of growth rate and celldensity 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 majorbiosynthetic 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. 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).

AB - 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 Saccharomycescerevisiae 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 productionhost known for its exceptional protein secretion capability. Interestingly, it exhibits a low growth rate protein production phenotype. We have used transcriptomics and proteomics to study the effect of growth rate and celldensity 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 majorbiosynthetic 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. 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).

U2 - 10.4148/1941-4765.1014

DO - 10.4148/1941-4765.1014

M3 - Conference abstract in proceedings

T3 - Fungal Genetics Reports

SP - 244

BT - Abstracts from the 11th European Conference on Fungal Genetics

PB - New Prairie Press

ER -

Arvas M, Pakula T, Smit B, Rautio J, Koivistoinen H, Jouhten P et al. Correlation of gene expression and protein production rate: A system wide study. In Abstracts from the 11th European Conference on Fungal Genetics. New Prairie Press. 2012. p. 244. PR8.52. (Fungal Genetics Reports; No. 6, Vol. 59). https://doi.org/10.4148/1941-4765.1014