Robust control of nitrogen assimilation by a bifunctional enzyme in E. coli

Yuval Hart, Daniel Madar, Jie Yuan, Anat Bren, Avraham E. Mayo, Joshua D. Rabinowitz, Uri Alon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Bacteria regulate the assimilation of multiple nutrients to enable growth. How is balanced utilization achieved, despite fluctuations in the concentrations of the enzymes that make up the regulatory circuitry? Here we address this question by studying the nitrogen system of E. coli. A mechanism based on the avidity of a bifunctional enzyme, adenylyltransferase (AT/AR), to its multimeric substrate, glutamine synthetase, is proposed to maintain a robust ratio between two key metabolites, glutamine and α-ketoglutarate. This ratio is predicted to be insensitive to variations in protein levels of the core circuit and to the rate of nitrogen utilization. We find using mass spectrometry that the metabolite ratio is robust to variations in protein levels and that this robustness depends on the bifunctional enzyme. Moreover, robustness carries through to the bacteria growth rate. Interrupting avidity by adding a monofunctional AT/AR mutant to the native system abolishes robustness, as predicted by the proposed mechanism.

Original languageEnglish
Pages (from-to)117-127
Number of pages11
JournalMolecular Cell
Volume41
Issue number1
DOIs
StatePublished - 7 Jan 2011
Externally publishedYes

Bibliographical note

Funding Information:
We thank H. Mori and the National BioResource Project (NIG, Japan) for the Keio collection. We thank A.J. Ninfa and P. Jiang for the AT-CDN plasmid. We thank N. Barkai, R. Milo, T. Tlusty, and G. Shinar for helpful discussions and insightful comments. This work was supported by the Israel Science Foundation, the Kahn Family Foundation, and the European Research Council.

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