Dynamic Control of Gene Expression with Riboregulated Switchable Feedback Promoters

One major challenge in synthetic biology is the deleterious impacts of cellular stress caused by expression of heterologous pathways, sensors, and circuits. Feedback control and dynamic regulation are broadly proposed strategies to mitigate this cellular stress by optimizing gene expression levels t...

Full description

Saved in:
Bibliographic Details
Published in:ACS synthetic biology 2021-05, Vol.10 (5), p.1199-1213
Main Authors: Glasscock, Cameron J, Biggs, Bradley W, Lazar, John T, Arnold, Jack H, Burdette, Lisa A, Valdes, Aliki, Kang, Min-Kyoung, Tullman-Ercek, Danielle, Tyo, Keith E J, Lucks, Julius B
Format: Article
Language:English
Subjects:
Escherichia coli - genetics
Escherichia coli - metabolism
Feedback, Physiological
Gene Expression
Gene Expression Regulation, Bacterial
Genes, Bacterial
Metabolic Engineering - methods
Metabolic Networks and Pathways - genetics
Operon
Promoter Regions, Genetic - genetics
Quorum Sensing - genetics
Riboswitch - genetics
Synthetic Biology - methods
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:One major challenge in synthetic biology is the deleterious impacts of cellular stress caused by expression of heterologous pathways, sensors, and circuits. Feedback control and dynamic regulation are broadly proposed strategies to mitigate this cellular stress by optimizing gene expression levels temporally and in response to biological cues. While a variety of approaches for feedback implementation exist, they are often complex and cannot be easily manipulated. Here, we report a strategy that uses RNA transcriptional regulators to integrate additional layers of control over the output of natural and engineered feedback responsive circuits. Called riboregulated switchable feedback promoters (rSFPs), these gene expression cassettes can be modularly activated using multiple mechanisms, from manual induction to autonomous quorum sensing, allowing control over the timing, magnitude, and autonomy of expression. We develop rSFPs in to regulate multiple feedback networks and apply them to control the output of two metabolic pathways. We envision that rSFPs will become a valuable tool for flexible and dynamic control of gene expression in metabolic engineering, biological therapeutic production, and many other applications.
ISSN:2161-5063
2161-5063
DOI:10.1021/acssynbio.1c00015