Chimeric LuxR transcription factors rewire natural product regulation.
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. Here, we show that exploiting the modular nature LuxR proteins, it is possible to construct functional chimeric LuxRs, which enable to both rewire quorum sensing systems and activate silent BGCs. Importantly, our strategy allowed to identify the novel natural product pseudomonol from a bacterium of the genus Pseudomonas.