Pseudomonas syringae is a soil-dwelling bacterium thatexhibits remarkable niche adaptability and it is known for its devastating impact as a plant pathogen. This bacterium has an outstanding capability to produce a wide array of biologically active natural products. P. syringae coexists with amoebal predators and fungal strains, which drives the production of secondary metabolites for predator evasion in addition to niche adaptation. In this study, we conducted a broad pangenomic analysis of 18 taxonomically distinct P. syringae strains leading to the identification of 231 biosyntheticgene clusters (BGCs). Among these, nonribosomal peptide synthetases (NRPSs) were particularly abundant, indicating their potential significance within this ecological context. We discovered and elucidated the structures of two novel classes of bioactive compounds, the syrilipamides and chlorosecimides. Furthermore, a bioinformatic analysis enabled the identification of an undescribed halogenase, SecA, essential for the chlorination of secimide A. We observed that syrilipamides and secimides and in particular mixtures thereof exhibit amoebicidal activities. Additionally, secimides showed selective antifungal activity. These findings provide valuable insights into the ecological roles of P. syringae natural products and highlighttheir potential for biotechnological applications and therapeuticdevelopment.