Massetolide F Synthesized by Pseudomonas extremorientalis YL19 Inhibits the Wheat Pathogenic Fungus Bipolaris...

Cyclic lipopeptides (CLPs), produced by diverse bacteria, including plant-associated Pseudomonas species, are bioactive metabolites with multiple functions that also benefit the host strain. Strain YL19, identified as Pseudomonas extremorientalis, showed strong antifungal activity against Bipolaris sorokiniana, the causal agent of wheat root rot. Its main secondary metabolite was purified through bioactivity-guided fractionation and identified as massetolide, marking the first report of its production by P. extremorientalis. In wheat pot experiments, the 100 mg massetolide F treatment reduced the disease index to 42.05, significantly lower than the diseased control. Massetolide F also displayed antitumor activity, with IC₅₀ values of 24 and 22 μg/mL against HeLa and HT1080 cells. Biosynthesis of massetolde F follows the classical Gac/Rsm pathway, but novel repressor of secondary metabolism (Rsm) binding sites were found in the 5'-UTR of luxRU and luxRD mRNA and LuxR regulators recognized unique promoter sequences unreported in other Pseudomonas that were identified, indicating a species-specific regulatory mechanism in YL19.