LuxR-type transcriptional activator proteins frequently flank bacterial biosynthetic gene clusters (BGCs) where they play a crucial role in regulating natural product formation. Only few bacterial BGCs are expressed under standard culturing conditions, thus modulation of flanking LuxRs is a powerful approach to activate silent clusters. Here, we show that exploiting the modular nature LuxR proteins and constructing chimeric LuxRs enables the activation of BGCs.