Studying of the regulatory roles of response regulators GlrR and ArcA in xenocoumacins biosynthesis in Xenorhabdus nematophila CB61

Xenocoumacins (Xcns), the major antimicrobial natural products produced by , have gained widespread attention for their potential application in crop protection. However, the regulatory mechanisms involved in the biosynthesis of Xcns remain poorly understood. In this study, we identified 21 potential two-component systems (TCSs) in CB6 by bioinformatic analysis. Among them, the response regulators (RRs) GlrR and ArcA were proven to positively regulate the production of Xcns based on gene deletion and complementation experiments. In addition, our results showed that GlrR played an important role in cell growth, while ArcA was involved in both cell morphology and growth. Using a variety of molecular biological and biochemical techniques, we found that GlrR controlled the Xcns biosynthesis by indirectly regulating the expression levels of the biosynthetic gene cluster (BGC). ArcA directly binded to the promoter regions of and to regulate the transcription of the Xcns BGC, and the binding sites were also identified. This study provides valuable insights into the regulatory network of Xcns biosynthesis, which will contribute to the construction of a high-yielding strain.