A Modular Receptor Platform To Expand the Sensing Repertoire of Bacteria.

Abstract:

:Engineered bacteria promise to revolutionize diagnostics and therapeutics, yet many applications are precluded by the limited number of detectable signals. Here we present a general framework to engineer synthetic receptors enabling bacterial cells to respond to novel ligands. These receptors are activated via ligand-induced dimerization of a single-domain antibody fused to monomeric DNA-binding domains (split-DBDs). Using E. coli as a model system, we engineer both transmembrane and cytosolic receptors using a VHH for ligand detection and demonstrate the scalability of our platform by using the DBDs of two different transcriptional regulators. We provide a method to optimize receptor behavior by finely tuning protein expression levels and optimizing interdomain linker regions. Finally, we show that these receptors can be connected to downstream synthetic gene circuits for further signal processing. The general nature of the split-DBD principle and the versatility of antibody-based detection should support the deployment of these receptors into various hosts to detect ligands for which no receptor is found in nature.

journal_name

ACS Synth Biol

journal_title

ACS synthetic biology

authors

Chang HJ,Mayonove P,Zavala A,De Visch A,Minard P,Cohen-Gonsaud M,Bonnet J

doi

10.1021/acssynbio.7b00266

subject

Has Abstract

pub_date

2018-01-19 00:00:00

pages

166-175

issue

1

issn

2161-5063

journal_volume

7

pub_type

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