Abstract
BackgroundGrowth 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.ResultsWe 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.ConclusionsBased 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).
Highlights
Growth rate is a major determinant of intracellular function
Chemostat cultivations In order to study the correlation of gene and protein expression with specific extracellular protein production rate (SPPR) we grew T. reesei in lactose limited chemostats in three conditions: specific constant growth rates of 0.03 h-1 (D03) and 0.06 h-1 (D06) with 10 g/L of lactose and 0.03 h-1 with 40 g/L lactose for higher cell density (HD)
Primary biosynthetic functions are expressed at low level in low growth rate protein production From analysis of distribution of correlation of gene expression to SPPR we found that genes in metabolism, protein secretion and known mitochondrial genes were generally expressed at low level when protein production rate was high in T. reesei (Figure 2)
Summary
Growth rate is a major determinant of intracellular function. 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 It exhibits a low growth rate protein production phenotype. The TOR (Target of Rapamycin) network links intra- and extra cellular signals to control the growth rate of S. cerevisiae. It regulates gene expression through a variety of transcription factors [1,6]. Nonsyntenic blocks are often found near telomers [15,17], where recombination rates can be high [10,16,18] and secreted, orphan [19] and paralogous genes [16] and single nucleotide polymorphisms [10] may be enriched
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