Chimeric LuxR Transcription Factors Rewire Natural Product Regulation

Angew Chem Int Ed Engl. 2020 Apr 6;59(15):6192-6195. doi: 10.1002/anie.201914449. Epub 2020 Feb 26.

Abstract

LuxR-type transcriptional activator proteins frequently regulate the expression of biosynthetic gene clusters (BGCs). With only a fraction of bacterial BGCs being expressed under standard culturing conditions, modulation of LuxRs would provide a powerful approach to activate silent clusters. We show that by exploiting the modular nature of LuxR proteins, it is possible to construct functional chimeric LuxRs, which enables both the rewiring of quorum sensing systems and the activation of silent BGCs. Importantly, our strategy allowed us to identify the novel natural product pseudomonol from a bacterium of the genus Pseudomonas.

Keywords: LuxRs; gene expression; natural products; quorum sensing; transcriptional activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / metabolism*
  • Genetic Engineering*
  • Multigene Family / genetics
  • Quorum Sensing
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*

Substances

  • Biological Products
  • Recombinant Proteins
  • Repressor Proteins
  • Trans-Activators
  • LuxR autoinducer binding proteins