Homologous Quorum Sensing Regulatory Circuit: A Dual-Input Genetic Controller for Modulating Quorum Sensing-Mediated Protein Expression in .

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TitleHomologous Quorum Sensing Regulatory Circuit: A Dual-Input Genetic Controller for Modulating Quorum Sensing-Mediated Protein Expression in .
Publication TypeJournal Article
Year of Publication2020
AuthorsHauk, P, Stephens, K, Virgile, C, VanArsdale, E, Pottash, AEli, Schardt, JS, Jay, SM, Sintim, HO, Bentley, WE
JournalACS Synth Biol
Volume9
Issue10
Pagination2692-2702
Date Published2020 Oct 16
ISSN2161-5063
Abstract

We developed a hybrid synthetic circuit that co-opts the genetic regulation of the native bacterial quorum sensing autoinducer-2 and imposes an extra external controller for maintaining tightly controlled gene expression. This dual-input genetic controller was mathematically modeled and, by design, can be operated in three modes: a constitutive mode that enables consistent and high levels of expression; a tightly repressed mode in which there is very little background expression; and an inducible mode in which concentrations of two signals (arabinose and autoinducer-2) determine the net amplification of the gene(s)-of-interest. We demonstrate the utility of the circuit for the controlled expression of human granulocyte macrophage colony stimulating factor in an engineered probiotic . This dual-input genetic controller is the first homologous AI-2 quorum sensing circuit that has the ability to be operated in three different modes. We believe it has the potential for wide-ranging biotechnological applications due its versatile features.

DOI10.1021/acssynbio.0c00179
Alternate JournalACS Synth Biol
PubMed ID32822530