Abstract
BackgroundFew genome-scale models of organisms focus on the regulatory networks and none of them integrates all known levels of regulation. In particular, the regulations involving metabolite pools are often neglected. However, metabolite pools link the metabolic to the genetic network through genetic regulations, including those involving effectors of transcription factors or riboswitches. Consequently, they play pivotal roles in the global organization of the genetic and metabolic regulatory networks.ResultsWe report the manually curated reconstruction of the genetic and metabolic regulatory networks of the central metabolism of Bacillus subtilis (transcriptional, translational and post-translational regulations and modulation of enzymatic activities). We provide a systematic graphic representation of regulations of each metabolic pathway based on the central role of metabolites in regulation. We show that the complex regulatory network of B. subtilis can be decomposed as sets of locally regulated modules, which are coordinated by global regulators.ConclusionThis work reveals the strong involvement of metabolite pools in the general regulation of the metabolic network. Breaking the metabolic network down into modules based on the control of metabolite pools reveals the functional organization of the genetic and metabolic regulatory networks of B. subtilis.
Highlights
Few genome-scale models of organisms focus on the regulatory networks and none of them integrates all known levels of regulation
We find that metabolite pools are strongly involved in regulation of the central metabolism of Bacillus subtilis, in agreement with the findings from an analysis of the genetic regulatory network of Escherichia coli [19]
Model construction Our aim was to study the general organization of the metabolic functions of B. subtilis, to identify the components involved in their regulations and to unravel how these regulations coordinate metabolism
Summary
Few genome-scale models of organisms focus on the regulatory networks and none of them integrates all known levels of regulation. Metabolite pools link the metabolic to the genetic network through genetic regulations, including those involving effectors of transcription factors or riboswitches They play pivotal roles in the global organization of the genetic and metabolic regulatory networks. The reconstruction and analysis of genome-scale genetic and metabolic regulatory networks has become an area of active research. It requires the integration of existing knowledge as a first step towards systems biology, which we define as the study of the interactions between the components of biological systems to understand how these interactions give rise to the function and behavior of (page number not for citation purposes). Metabolites can modulate the activity of transcription factors and enzymes and are key regulators
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