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

ACS Synth Biol. 2020 Oct 16;9(10):2692-2702. doi: 10.1021/acssynbio.0c00179. Epub 2020 Sep 15.


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 E. coli. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acyl-Butyrolactones / metabolism
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism*
  • Gene Expression
  • Gene Expression Regulation, Bacterial
  • Gene Regulatory Networks*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / isolation & purification
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Homoserine / analogs & derivatives
  • Homoserine / metabolism
  • Humans
  • Lactones / metabolism
  • Metabolic Engineering / methods*
  • Microorganisms, Genetically-Modified
  • Plasmids / genetics
  • Quorum Sensing / genetics*
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Signal Transduction / genetics*


  • Acyl-Butyrolactones
  • Lactones
  • N-octanoylhomoserine lactone
  • Recombinant Proteins
  • Homoserine
  • Granulocyte-Macrophage Colony-Stimulating Factor