Growth control of the eukaryote cell: a systems biology study in yeast.

BACKGROUND: Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. RESULTS: Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. CONCLUSION: This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Transcriptional response of Pseudomonas aeruginosa to a phosphate-deficient Lolium perenne rhizosphere

Background and aims Plant-bacterial interactions in the rhizosphere are important in mediating soil nutrient transformations. Plants supply carbon-rich substrates to rhizobacteria as root exudates and bacteria mobilise soil-bound phosphate for plant nutrition. This study aimed to probe the specificity of the plant effect on bacterial gene expression in Pstarved rhizosphere conditions. Methods DNA microarrays were employed to study gene expression in the rhizosphere of Lolium perenne grown under high and low phosphate regimes (330 ?M vs. 3-6 ?M phosphate). Root exudation under these regimes was also quantified. Phosphateregulated gene expression of a panel of 22 genes was compared in rhizosphere, planktonic culture and during biofilm growth on an artificial root. Results Plant growth and root exudation were affected by P-availability. P-limited conditions induced increased expression of bacterial genes of an aromatic degradation pathway (catA), heavy metal sensing (PA2523), and membrane proteins (glpM, crcB), while genes involved in cell motility and amino acid uptake/ metabolism were downregulated. A crcB mutant was impaired in rhizosphere survival under low phosphate conditions, though glpM and catA mutants were not affected. Several of the genes studied were induced by phosphate limitation in all three lifestyles studied. Conclusions Our results show the importance of the plant-microbe interaction in controlling the bacterial transcriptional response in a phosphate-limited rhizosphere. (Résumé d'auteur

Transcriptional response of Pseudomonas aeruginosa to a phosphate-deficient Lolium perenne rhizosphere

Background and aims: Plant-bacterial interactions in the rhizosphere are important in mediating soil nutrient transformations. Plants supply carbon-rich substrates to rhizobacteria as root exudates and bacteria mobilise soil-bound phosphate for plant nutrition. This study aimed to probe the specificity of the plant effect on bacterial gene expression in P-starved rhizosphere conditions. Methods: DNA microarrays were employed to study gene expression in the rhizosphere of Lolium perenne grown under high and low phosphate regimes (330 μM vs. 3–6 μM phosphate). Root exudation under these regimes was also quantified. Phosphate-regulated gene expression of a panel of 22 genes was compared in rhizosphere, planktonic culture and during biofilm growth on an artificial root. Results: Plant growth and root exudation were affected by P-availability. P-limited conditions induced increased expression of bacterial genes of an aromatic degradation pathway (catA), heavy metal sensing (PA2523), and membrane proteins (glpM, crcB), while genes involved in cell motility and amino acid uptake/ metabolism were downregulated. A crcB mutant was impaired in rhizosphere survival under low phosphate conditions, though glpM and catA mutants were not affected. Several of the genes studied were induced by phosphate limitation in all three lifestyles studied. Conclusions: Our results show the importance of the plant-microbe interaction in controlling the bacterial transcriptional response in a phosphate-limited rhizosphere

Integration of proteome and metabolic control to show regulation of carbon and nitrogen metabolic fluxes at the protein (enzyme) level

Shown here are the coupling of carbon and nitrogen fluxes at the level of glutamate dehydrogenase (Gdh1p, Gdh2p) and glutamine synthetase (Gln1p), the regulation of arginine biosynthesis at the carbamoyl phosphate synthetase (Cpa1p, Cpa2p) level and amino-acid biosynthesis, and amino-acid sensing by TOR. Selected proteins with levels consistently upregulated (red) with growth independently of culture conditions are shown. Enzymes responsible for the cytosolic 2-oxoglutarate pool: Aco1p and Aco2p, aconitase and putative aconitase isoenzyme; Odc1p and Odc2p, mitochondrial 2-oxoglutarate transporters; Idp2p, NADP-specific isocitrate dehydrogenase. Enzyme subunits coupling the oxidation of succinate to the transfer of electrons to ubiquinone: Sdh1p and Sdh2p, succinate dehydrogenase, flavoprotein, and iron-sulfur protein subunits, respectively. Metabolic diagram from [42, 91, 92] and drawn using Cell Designer [136] and Adobe Illustrator [137].<p><b>Copyright information:</b></p><p>Taken from "Growth control of the eukaryote cell: a systems biology study in yeast"</p><p>http://jbiol.com/content/6/2/4</p><p>Journal of Biology 2007;6(2):4-4.</p><p>Published online 30 Apr 2007</p><p>PMCID:PMC2373899.</p><p></p

Integration of proteome and metabolic control to show regulation of sulfur and C1 (folate) metabolic fluxes at the protein (enzyme) level

Selected proteins with levels consistently upregulated (red) or downregulated (green) with growth independently of culture conditions are shown. Sulfur, C1 metabolism, methyl cycle, methionine and -adenosylmethionine (SAM) fluxes towards methylation of proteins, rRNAs and tRNAs, and protein biosynthesis are shown here. Metabolic pathways and enzymes are from [42,82, 103-105] and the diagram is drawn with Cell Designer [136] and Adobe Illustrator [137]. Reverse methionine biosynthetic pathways [83] have been omitted for clarity. Metabolite abbreviations: THF, tetrahydrofolate; METTHF, 5,10-methylenetetrahydrofolate; MTHPTGLUT, 5-methyltetrahydropteroyltriglutamate (donor of the terminal methyl group in methionine biosynthesis); GT, glutathione; CYS, cysteine; CT, cystathionine; OAHS, -acetylhomoserine; HCYS, homocysteine; MET, methionine; SAM, -adenosylmethionine; SAH, -adenosylhomocysteine; D-SAM, decarboxylated -adenosylmethionine; MTA, methylthioadenosine. Metabolic steps (genes/enzymes): Met10p, sulfite reductase alpha subunit; Ecm17p, sulfite reductase beta subunit; , folylpolyglutamate synthetase (Met7p not detected; the relevance of polyglutamylation in the C1 metabolism branch was demonstrated at the transcriptional level (see text)); Met13p, methylenetetrahydrofolate reductase isozyme; Met6p, methionine synthase; Mes1p, methionyl-tRNA synthetase; Sam1p, S-adenosylmethionine synthetase isozyme; Sam2p, S-adenosylmethionine synthetase isozyme. Sah1p, S-adenosyl-L-homocysteine hydrolase; Ado1p, adenosine kinase.<p><b>Copyright information:</b></p><p>Taken from "Growth control of the eukaryote cell: a systems biology study in yeast"</p><p>http://jbiol.com/content/6/2/4</p><p>Journal of Biology 2007;6(2):4-4.</p><p>Published online 30 Apr 2007</p><p>PMCID:PMC2373899.</p><p></p