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).
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 language | English |
|---|---|
| Title of host publication | Abstracts from the 11th European Conference on Fungal Genetics |
| Publisher | New Prairie Press |
| Pages | 244 |
| Publication status | Published - 2012 |
| MoE publication type | Not Eligible |
| Event | 11th European Conference on Fungal Genetics - Marburg, Germany Duration: 30 Mar 2012 → 2 Apr 2012 |
Publication series
| Series | Fungal Genetics Reports |
|---|---|
| Number | 6 |
| Volume | 59 |
| ISSN | 1941-4757 |
Conference
| Conference | 11th European Conference on Fungal Genetics |
|---|---|
| Country/Territory | Germany |
| City | Marburg |
| Period | 30/03/12 → 2/04/12 |