Prediction of Regulatory Pathways from Environmental Signals to BGCs Expression

Actinobacteria are prolific producers of bioactive Specialized Metabolites (SMs), synthesized by Biosynthetic Gene Clusters (BGCs). The expression of these BGCs is tightly regulated by Transcription Factors (TFs) in response to environmental cues. However, many cryptic BGCs remain silent under laboratory conditions, largely due to limited understanding of the regulatory mechanisms and the complexity of the ecological niches in which these bacteria reside.
To address this challenge and facilitate the identification of environmental cues that control BGCs expression, we developed the COMMBAT software, a bioinformatic tool that predicts TF biding sites (TFBSs) within BGCs. We applied COMMBAT to global TFs and aim to validate series of new signaling pathways using Mass Spectrometry Imaging (MSI), revealing novel regulatory links between environmental signals and SMs production. In parallel, we aim to unveil a novel metabolic route leading to BGCs expression associated with a yet unknown environmental signal using nano Differential Scanning Fluorimetry (nanoDSF).