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Updated: Jan 12, 2026
09:08
From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
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Global profiling of polyketide synthases in facultative multicellular eukaryotes.
Markus Günther1, Rosa Herbst1, Nico Ueberschaar2
1Department of Paleobiotechnology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena D-07745, Germany.
Summary
Disrupting the DiSfp gene in Dictyostelium discoideum halted polyketide production, impacting growth, cell movement, and spore formation. This reveals polyketides
Area of Science:
- Molecular Biology
- Biochemistry
- Natural Product Discovery
Background:
- Polyketides are diverse natural products with significant biological roles.
- Dictyostelium discoideum possesses 40 polyketide synthase (PKS) genes with largely unknown functions.
- PKS activation requires the phosphopantetheinyl transferase DiSfp.
Purpose of the Study:
- To investigate the functional role of DiSfp and PKS-derived metabolites in Dictyostelium discoideum.
- To understand the contribution of polyketides to cellular physiology and development.
Main Methods:
- Gene disruption of DiSfp in Dictyostelium discoideum.
- Integrated phenotypic, transcriptomic, and metabolomic analyses.
- Comparative metabolomic profiling of wild-type and mutant strains.
Main Results:
- DiSfp disruption abolished polyketide metabolite production.
- Mutants exhibited impaired growth, defective macropinocytosis, aberrant chemotaxis, and reduced spore formation.
- Candidate polyketide metabolites were identified across developmental stages.
Conclusions:
- Polyketides are essential for Dictyostelium discoideum's growth, cellular processes, and development.
- This study establishes a functional link between PKS machinery and metabolic/developmental networks.
- Provides a resource for future polyketide discovery in Dictyostelium.
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