Global profiling of polyketide synthases in facultative multicellular eukaryotes

• 成果类型: Article
• 署名作者: Gunther, Markus; Herbst, Rosa; Ueberschaar, Nico; Hildebrandt, Daniela; Reimer, Lisa; Stallforth, Pierre
• 署名单位: Leibniz Association; Hans Knoll Institute (HKI); Friedrich Schiller University of Jena; Friedrich Schiller University of Jena; Friedrich Schiller University of Jena
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2515852122
• 发表日期: 2025-11-11
• 页码: e2515852122
• 关键词: polyketide synthases; secondary metabolism; social amoebae; phosphopantetheinyl transferase; DIFFERENTIATION-INDUCING FACTOR; green fluorescent protein; dictyostelium-discoideum; cell-differentiation; r package; gene; biosynthesis; DIF-1; identification; receptor

摘要

Polyketides represent a structurally diverse class of natural products with a wide range of biological functions, including antimicrobial activity, defense responses, developmental regulation, pigmentation, and intercellular and intracellular communication signals. The the specific and collective functions remain poorly understood. PKSs require activation by the phosphopantetheinyl transferase DiSfp, which converts inactive apoenzymes into functional holo forms. Disruption of the DiSfp gene 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, associated with altered expression of genes regulating these processes. Comparative metabolomic profiling of the mutant identified candidate polyketide metabolites across different developmental stages, providing a valuable resource for targeted identification and isolation of previously undescribed compounds. This study establishes a functional discoideum, highlighting the essential roles of polyketides in cellular physiology and offering a framework for future polyketide discovery.