Modular, Multi-Input Transcriptional Logic Gating with Orthogonal LacI/GalR Family Chimeras

  • Shis D
  • Hussain F
  • Meinhardt S
 et al. 
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In prokaryotes, the construction of synthetic, multi-input promoters is constrained by the number of transcription factors that can simultaneously regulate a single promoter. This fundamental engineering constraint is an obstacle to synthetic biologists because it limits the computational capacity of engineered gene circuits. Here, we demonstrate that complex multi-input transcriptional logic gating can be achieved through the use of ligand-inducible chimeric transcription factors assembled from the {LacI/GalR} family. These modular chimeras each contain a ligand-binding domain and a {DNA-binding} domain, both of which are chosen from a library of possibilities. When two or more chimeras have the same {DNA-binding} domain, they independently and simultaneously regulate any promoter containing the appropriate operator site. In this manner, simple transcriptional {AND} gating is possible through the combination of two chimeras, and multiple-input {AND} gating is possible with the simultaneous use of three or even fou...

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  • David L. Shis

  • Faiza Hussain

  • Sarah Meinhardt

  • Liskin Swint-Kruse

  • Matthew R. Bennett

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