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Fundamental design principles for transcription-factor-based metabolite biosensors

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Mannan, Ahmad A., Liu, Di, Zhang, Fuzhong and Oyarzún, Diego A. (2017) Fundamental design principles for transcription-factor-based metabolite biosensors. ACS Synthetic Biology, 6 (10). pp. 1851-1859. doi:10.1021/acssynbio.7b00172 ISSN 2161-5063.

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Official URL: https://doi.org/10.1021/acssynbio.7b00172

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Abstract

Metabolite biosensors are central to current efforts toward precision engineering of metabolism. Although most research has focused on building new biosensors, their tunability remains poorly understood and is fundamental for their broad applicability. Here we asked how genetic modifications shape the dose–response curve of biosensors based on metabolite-responsive transcription factors. Using the lac system in Escherichia coli as a model system, we built promoter libraries with variable operator sites that reveal interdependencies between biosensor dynamic range and response threshold. We developed a phenomenological theory to quantify such design constraints in biosensors with various architectures and tunable parameters. Our theory reveals a maximal achievable dynamic range and exposes tunable parameters for orthogonal control of dynamic range and response threshold. Our work sheds light on fundamental limits of synthetic biology designs and provides quantitative guidelines for biosensor design in applications such as dynamic pathway control, strain optimization, and real-time monitoring of metabolism.

Item Type: Journal Article
Subjects: Q Science > QA Mathematics
Q Science > QP Physiology
Q Science > QR Microbiology
Divisions: Faculty of Science, Engineering and Medicine > Engineering > Engineering
Library of Congress Subject Headings (LCSH): Metabolites, Biosensors -- Genetics, Transcription factors, Escherichia coli
Journal or Publication Title: ACS Synthetic Biology
Publisher: American Chemical Society
ISSN: 2161-5063
Official Date: 20 October 2017
Dates:
DateEvent
20 October 2017Published
1 August 2017Available
1 August 2017Accepted
25 May 2017Submitted
Volume: 6
Number: 10
Page Range: pp. 1851-1859
DOI: 10.1021/acssynbio.7b00172
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Date of first compliant deposit: 1 June 2018
Date of first compliant Open Access: 1 August 2018
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
RGY0076-2015Human Frontier Science Programhttp://dx.doi.org/10.13039/100004412
MCB1453147National Science Foundationhttp://dx.doi.org/10.13039/100000001
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