Transcriptomic analysis of PPTAse ko mutant
Polyketides represent a structurally and functionally diverse class of natural products with diverse biological functions, including antimicrobial activity, defense responses, developmental regulation, pigmentation, and both intercellular and intracellular communication signals. The social amoeba Dictyostelium discoideum harbors more than 40 polyketide synthase (PKS) genes, yet the specific and collective functions of most remain poorly understood. PKSs require activation by the phosphopantetheinyl transferase DiSfp, which converts inactive apoenzymes into their functional holo forms. Disruption of the gene encoding DiSfp abolished the production of PKS-derived metabolites across all developmental stages. Integrated phenotypic, transcriptomic, and metabolomic analyses revealed impaired growth in liquid culture, defects in macropinocytosis, aberrant chemotaxis, and diminished spore formation, all associated with altered expression of genes regulating these processes. Comparative metabolomic profiling of the mutant identified numerous candidate polyketide metabolites across different developmental stages, providing a valuable resource for the targeted identification and isolation of novel compounds. This study establishes a functional link between the PKS enzymatic machinery and the metabolic and developmental networks of D. discoideum, highlighting the essential roles of polyketides in cellular physiology and offering a framework for future polyketide discovery.