Biosensor libraries harness large classes of binding domains for construction of allosteric transcriptional regulators

The ability of bacteria to sense specific molecules within their environment and trigger metabolic responses in accordance is an invaluable biotechnological resource. While many transcription factors (TFs) mediating such processes have been studied, only a handful have been leveraged for molecular b...

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Bibliographic Details
Published in:Nature communications 2018-08, Vol.9 (1), p.3101-12, Article 3101
Main Authors: Juárez, Javier F., Lecube-Azpeitia, Begoña, Brown, Stuart L., Johnston, Christopher D., Church, George M.
Format: Article
Language:English
Subjects:
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38/23
38/35
42/40
60 APPLIED LIFE SCIENCES
631/1647/1888
631/326/171
631/553/552
96/31
Allosteric properties
Allosteric Regulation
Allosteric Site
BASIC BIOLOGICAL SCIENCES
Benzoates - chemistry
Binding
Biosensing Techniques
Biosensors
Biotechnology
Cloning, Molecular
Deoxyribonucleic acid
DNA
Escherichia coli
Flow Cytometry
Gene expression
Gene Library
Gene Regulatory Networks
Genes, Reporter
Genetic Vectors
Humanities and Social Sciences
Kinases
Ligands
Lignin
Metabolites
Molecular biology
multidisciplinary
Phosphorylation
Plasmids - metabolism
Protein Binding
Protein Domains
Proteins
Regulators
RNA polymerase
Science
Science (multidisciplinary)
Sensors
Signal transduction
Transcription factors
Transcription Factors - metabolism
Transcription, Genetic
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Summary:The ability of bacteria to sense specific molecules within their environment and trigger metabolic responses in accordance is an invaluable biotechnological resource. While many transcription factors (TFs) mediating such processes have been studied, only a handful have been leveraged for molecular biology applications. To expand the repertoire of biotechnologically relevant sensors we present a strategy for the construction and testing of chimeric TF libraries, based on the fusion of highly soluble periplasmic binding proteins (PBPs) with DNA-binding domains (DBDs). We validate this concept by constructing and functionally testing two unique sense-and-respond regulators for benzoate, an environmentally and industrially relevant metabolite. This work will enable the development of tailored biosensors for novel synthetic regulatory circuits. Bacterially encoded environmental sensor proteins are potentially a rich source of transcriptional control but only a few have been harnessed for biotechnological applications. Here the authors develop a general strategy for designing custom-made monogenic synthetic sensors and validate the approach by designing two sense-and-respond regulators for benzoate.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-05525-6