Functional characterization of alternate optimal solutions of escherichia coli's transcriptional and translational machinery

Ines Thiele*, Ronan M.T. Fleming, Aarash Bordbar, Jan Schellenberger, Bernhard Palsson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

The constraint-based reconstruction and analysis approach has recently been extended to describe Escherichia coli's transcriptional and translational machinery. Here, we introduce the concept of reaction coupling to represent the dependency between protein synthesis and utilization. These coupling constraints lead to a significant contraction of the feasible set of steady-state fluxes. The subset of alternate optimal solutions (AOS) consistent with maximal ribosome production was calculated. The majority of transcriptional and translational reactions were active for all of these AOS, showing that the network has a low degree of redundancy. Furthermore, all calculated AOS contained the qualitative expression of at least 92% of the known essential genes. Principal component analysis of AOS demonstrated that energy currencies (ATP, GTP, and phosphate) dominate the network's capability to produce ribosomes. Additionally, we identified regulatory control points of the network, which include the transcription reactions of σ70 (RpoD) as well as that of a degradosome component (Rne) and of tRNA charging (ValS). These reactions contribute significant variance among AOS. These results show that constraint-based modeling can be applied to gain insight Into the systemic properties of E. coli's transcriptional and translational machinery.

Original languageEnglish
Pages (from-to)2072-2081
Number of pages10
JournalBiophysical Journal
Volume98
Issue number10
DOIs
Publication statusPublished - 19 May 2010

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health (grant No. R0157089) and the Department of Energy (award No. DE-SC00092009).

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