Engineering repressors with coevolutionary cues facilitates toggle switches with a master reset.

ABSTRACT: Engineering allosteric transcriptional repressors containing an environmental sensing module (ESM) and a DNA recognition module (DRM) has the potential to unlock a combinatorial set of rationally designed biological responses. We demonstrated that constructing hybrid repressors by fusing distinct ESMs and DRMs provides a means to flexibly rewire genetic networks for complex signal processing. We have used coevolutionary traits among LacI homologs to develop a model for predicting compatibility between ESMs and DRMs. Our predictions accurately agree with the performance of 40 engineered repressors. We have harnessed this framework to develop a system of multiple toggle switches with a master OFF signal that produces a unique behavior: each engineered biological activity is switched to a sta

SUBMITTER: Dimas RP 

PROVIDER: S-EPMC6547410 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature