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Dissecting specific and global transcriptional regulation of bacterial gene expression
(2013)Molecular Systems BiologyGene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional—but often neglected—layer of complexity in gene expression. Here, we develop an experimental‐computational approach to dissect specific and global regulation in the bacterium Escherichia coli. By using fluorescent promoter reporters, ...Journal Article -
Temporal system-level organization of the switch from glycolytic to gluconeogenic operation in yeast
(2013)Molecular Systems BiologyThe diauxic shift in Saccharomyces cerevisiae is an ideal model to study how eukaryotic cells readjust their metabolism from glycolytic to gluconeogenic operation. In this work, we generated time‐resolved physiological data, quantitative metabolome (69 intracellular metabolites) and proteome (72 enzymes) profiles. We found that the diauxic shift is accomplished by three key events that are temporally organized: (i) a reduction in the ...Journal Article -
Transcriptional regulation is insufficient to explain substrate‐induced flux changes in Bacillus subtilis
(2013)Molecular Systems BiologyOne of the key ways in which microbes are thought to regulate their metabolism is by modulating the availability of enzymes through transcriptional regulation. However, the limited success of efforts to manipulate metabolic fluxes by rewiring the transcriptional network has cast doubt on the idea that transcript abundance controls metabolic fluxes. In this study, we investigate control of metabolic flux in the model bacterium Bacillus ...Journal Article -
Regulation of yeast central metabolism by enzyme phosphorylation
(2012)Molecular Systems BiologyAs a frequent post‐translational modification, protein phosphorylation regulates many cellular processes. Although several hundred phosphorylation sites have been mapped to metabolic enzymes in Saccharomyces cerevisiae, functionality was demonstrated for few of them. Here, we describe a novel approach to identify in vivo functionality of enzyme phosphorylation by combining flux analysis with proteomics and phosphoproteomics. Focusing on ...Journal Article -
Large-scale 13C-flux analysis reveals distinct transcriptional control of respiratory and fermentative metabolism in Escherichia coli
(2011)Molecular Systems BiologyDespite our increasing topological knowledge on regulation networks in model bacteria, it is largely unknown which of the many co‐occurring regulatory events actually control metabolic function and the distribution of intracellular fluxes. Here, we unravel condition‐dependent transcriptional control of Escherichia coli metabolism by large‐scale 13C‐flux analysis in 91 transcriptional regulator mutants on glucose and galactose. In contrast ...Journal Article -
Comprehensive quantitative analysis of central carbon and amino-acid metabolism in Saccharomyces cerevisiae under multiple conditions by targeted proteomics
(2011)Molecular Systems BiologyDecades of biochemical research have identified most of the enzymes that catalyze metabolic reactions in the yeast Saccharomyces cerevisiae. The adaptation of metabolism to changing nutritional conditions, in contrast, is much less well understood. As an important stepping stone toward such understanding, we exploit the power of proteomics assays based on selected reaction monitoring (SRM) mass spectrometry to quantify abundance changes ...Journal Article -
Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity
(2010)Molecular Systems BiologyWhat is the relationship between enzymes and metabolites, the two major constituents of metabolic networks? We propose three alternative relationships between enzyme capacity and metabolite concentration alterations based on a Michaelis–Menten kinetic; that is enzyme capacities, metabolite concentrations, or both could limit the metabolic reaction rates. These relationships imply different correlations between changes in enzyme capacity ...Journal Article -
Unraveling condition-dependent networks of transcription factors that control metabolic pathway activity in yeast
(2010)Molecular Systems BiologyWhich transcription factors control the distribution of metabolic fluxes under a given condition? We address this question by systematically quantifying metabolic fluxes in 119 transcription factor deletion mutants of Saccharomyces cerevisiae under five growth conditions. While most knockouts did not affect fluxes, we identified 42 condition‐dependent interactions that were mediated by a total of 23 transcription factors that control ...Journal Article