title: A synthetic growth switch based on controlled expression of RNA polymerase.
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.
authors.affiliation: Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Saint Martin d'Hères, France INRIA, Grenoble - Rhône-Alpes research center, Saint Ismier, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Izard
authors.affiliation: Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Saint Martin d'Hères, France INRIA, Grenoble - Rhône-Alpes research center, Saint Ismier, France.
authors.forename: Cindy D C
authors.initials: CD
authors.lastname: Gomez Balderas
authors.affiliation: INRIA, Grenoble - Rhône-Alpes research center, Saint Ismier, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Ropers
authors.affiliation: Université Grenoble Alpes, Laboratoire Interdisciplinaire de Physique (CNRS UMR 5588), Saint Martin d'Hères, France INRIA, Grenoble - Rhône-Alpes research center, Saint Ismier, France.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lacour
authors.affiliation: Center for Research and Interdisciplinarity, INSERM U1001, Medicine Faculty, Site Cochin Port-Royal, University Paris Descartes, Paris, France.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Song
authors.affiliation: Center for Research and Interdisciplinarity, INSERM U1001, Medicine Faculty, Site Cochin Port-Royal, University Paris Descartes, Paris, France.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Center for Research and Interdisciplinarity, INSERM U1001, Medicine Faculty, Site Cochin Port-Royal, University Paris Descartes, Paris, France.
authors.forename: Ariel B
authors.initials: AB
authors.lastname: Lindner
authors.affiliation: 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.
authors.forename: Johannes
authors.initials: J
authors.lastname: Geiselmann
authors.affiliation: INRIA, Grenoble - Rhône-Alpes research center, Saint Ismier, France hans.geiselmann@ujf-grenoble.fr hidde.de-jong@inria.fr.
authors.forename: Hidde
authors.initials: H
authors.lastname: de Jong
mesh_terms: D012321:DNA-Directed RNA Polymerases / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development* / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D058615:Synthetic Biology / Q000379:methods*; D049490:Systems Biology
chemical_list: D012321:DNA-Directed RNA Polymerases
keywords: RNA polymerase; bacterial physiology; biotechnology; growth; synthetic biology