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Modular Riboswitch Toolsets for Synthetic Genetic Control in Diverse Bacterial Species

DOI: 10.1021/ja502873j DOI Help
PMID: 24971878 PMID Help

Authors: Christopher J. Robinson (The University of Manchester) , Helen A. Vincent (The University of Manchester) , Ming-cheng Wu (The University of Manchester) , P Lowe (The University of Manchester) , Mark Dunstan (University of Manchester) , David Leys (School of Chemistry & Manchester Interdisciplinary Biocentre, The University of Manchester) , Jason Micklefield (The University of Manchester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of The American Chemical Society , VOL 136 (30) , PAGES 10615 - 10624

State: Published (Approved)
Published: July 2014
Diamond Proposal Number(s): 8997

Open Access Open Access

Abstract: Ligand-dependent control of gene expression is essential for gene functional analysis, target validation, protein production, and metabolic engineering. However, the expression tools currently available are difficult to transfer between species and exhibit limited mechanistic diversity. Here we demonstrate how the modular architecture of purine riboswitches can be exploited to develop orthogonal and chimeric switches that are transferable across diverse bacterial species, modulating either transcription or translation, to provide tunable activation or repression of target gene expression, in response to synthetic non-natural effector molecules. Our novel riboswitch–ligand pairings are shown to regulate physiologically important genes required for bacterial motility in Escherichia coli and cell morphology in Bacillus subtilis. These findings are relevant for future gene function studies and antimicrobial target validation, while providing new modular and orthogonal regulatory components for deployment in synthetic biology regimes.

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I04-Macromolecular Crystallography