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Burden-driven feedback control of gene expression

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Title: Burden-driven feedback control of gene expression
Authors: Ceroni, F
Boo, A
Furini, S
Gorochowski, T
Ladak, Y
Awan, A
Gilbert, C
Stan, G
Ellis, T
Item Type: Journal Article
Abstract: Cells use feedback regulation to ensure robust growth despite fluctuating demands for resources and differing environmental conditions. However, the expression of foreign proteins from engineered constructs is an unnatural burden that cells are not adapted for. Here we combined RNA-seq with an in vivo assay to identify the major transcriptional changes that occur in Escherichia coli when inducible synthetic constructs are expressed. We observed that native promoters related to the heat-shock response activated expression rapidly in response to synthetic expression, regardless of the construct. Using these promoters, we built a dCas9-based feedback-regulation system that automatically adjusts the expression of a synthetic construct in response to burden. Cells equipped with this general-use controller maintained their capacity for native gene expression to ensure robust growth and thus outperformed unregulated cells in terms of protein yield in batch production. This engineered feedback is to our knowledge the first example of a universal, burden-based biomolecular control system and is modular, tunable and portable.
Issue Date: 26-Mar-2018
Date of Acceptance: 15-Feb-2018
URI: http://hdl.handle.net/10044/1/57105
DOI: https://dx.doi.org/10.1038/nmeth.4635
ISSN: 1548-7091
Publisher: Nature Publishing Group
Start Page: 387
End Page: 393
Journal / Book Title: Nature Methods
Volume: 15
Copyright Statement: © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: EP/J021849/1
EP/M002306/1
EP/M002187/1
EP/P009352/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemical Research Methods
Biochemistry & Molecular Biology
HEAT-SHOCK RESPONSE
ESCHERICHIA-COLI
SYNTHETIC BIOLOGY
RNA-SEQ
TRADE-OFFS
GROWTH
PROTEIN
CIRCUITS
BACTERIA
VISUALIZATION
06 Biological Sciences
10 Technology
11 Medical And Health Sciences
Developmental Biology
Publication Status: Published
Embargo Date: 2019-09-26
Appears in Collections:Faculty of Engineering
Bioengineering
Chemical Engineering



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