Correlation of gene expression and protein production rate

a system wide study

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

Research output: Contribution to journalArticleScientificpeer-review

43 Citations (Scopus)

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).

Original languageEnglish
Article number616
JournalBMC Genomics
Volume12
DOIs
Publication statusPublished - 20 Dec 2011
MoE publication typeA1 Journal article-refereed

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Gene Expression
Proteins
Growth
Hypocrea
Secondary Metabolism
Trichoderma
Glycolysis
Proteomics
Saccharomyces cerevisiae
Intercellular Signaling Peptides and Proteins
Fungi
Cell Count
Genome
Phenotype
Genes

Cite this

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

In: BMC Genomics, Vol. 12, 616, 20.12.2011.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

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

N1 - CA2: TK402 SDA: BIC ISI: BIOTECHNOLOGY & APPLIED MICROBIOLOGY

PY - 2011/12/20

Y1 - 2011/12/20

N2 - 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).

AB - 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).

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DO - 10.1186/1471-2164-12-616

M3 - Article

VL - 12

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

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