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Mol Syst Biol. 2015 Nov 23;11(11):840. doi: 10.15252/msb.20156382.

A synthetic growth switch based on controlled expression of RNA polymerase.

Author information

1
Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Saint Martin d'Hères, France INRIA, Grenoble - Rhône-Alpes research center, Saint Ismier, France.
2
INRIA, Grenoble - Rhône-Alpes research center, Saint Ismier, France.
3
Center for Research and Interdisciplinarity, INSERM U1001, Medicine Faculty, Site Cochin Port-Royal, University Paris Descartes, Paris, France.
4
Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Saint Martin d'Hères, France INRIA, Grenoble - Rhône-Alpes research center, Saint Ismier, France hans.geiselmann@ujf-grenoble.fr hidde.de-jong@inria.fr.
5
INRIA, Grenoble - Rhône-Alpes research center, Saint Ismier, France hans.geiselmann@ujf-grenoble.fr hidde.de-jong@inria.fr.

Abstract

The ability to control growth is essential for fundamental studies of bacterial physiology and biotechnological applications. We have engineered an Escherichia coli strain in which the transcription of a key component of the gene expression machinery, RNA polymerase, is under the control of an inducible promoter. By changing the inducer concentration in the medium, we can adjust the RNA polymerase concentration and thereby switch bacterial growth between zero and the maximal growth rate supported by the medium. We show that our synthetic growth switch functions in a medium-independent and reversible way, and we provide evidence that the switching phenotype arises from the ultrasensitive response of the growth rate to the concentration of RNA polymerase. We present an application of the growth switch in which both the wild-type E. coli strain and our modified strain are endowed with the capacity to produce glycerol when growing on glucose. Cells in which growth has been switched off continue to be metabolically active and harness the energy gain to produce glycerol at a twofold higher yield than in cells with natural control of RNA polymerase expression. Remarkably, without any further optimization, the improved yield is close to the theoretical maximum computed from a flux balance model of E. coli metabolism. The proposed synthetic growth switch is a promising tool for gaining a better understanding of bacterial physiology and for applications in synthetic biology and biotechnology.

KEYWORDS:

RNA polymerase; bacterial physiology; biotechnology; growth; synthetic biology

PMID:
26596932
PMCID:
PMC4670729
DOI:
10.15252/msb.20156382
[Indexed for MEDLINE]
Free PMC Article

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