RRC ID 76379
Author Günther M, Reimer C, Herbst R, Kufs JE, Rautschek J, Ueberschaar N, Zhang S, Peschel G, Reimer L, Regestein L, Valiante V, Hillmann F, Stallforth P.
Title Yellow polyketide pigment suppresses premature hatching in social amoeba.
Journal Proc Natl Acad Sci U S A
Abstract Low-molecular-weight natural products from microbes are indispensable in the development of potent drugs. However, their biological roles within an ecological context often remain elusive. Here, we shed light on natural products from eukaryotic microorganisms that have the ability to transition from single cells to multicellular organisms: the social amoebae. These eukaryotes harbor a large number of polyketide biosynthetic genes in their genomes, yet virtually none of the corresponding products can be isolated or characterized. Using complementary molecular biology approaches, including CRISPR-Cas9, we generated polyketide synthase (pks5) inactivation and overproduction strains of the social amoeba Dictyostelium discoideum. Differential, untargeted metabolomics of wild-type versus mutant fruiting bodies allowed us to pinpoint candidate metabolites derived from the amoebal PKS5. Extrachromosomal expression of the respective gene led to the identification of a yellow polyunsaturated fatty acid. Analysis of the temporospatial production pattern of this compound in conjunction with detailed bioactivity studies revealed the polyketide to be a spore germination suppressor.
Volume 119(43)
Pages e2116122119
Published 2022-10-25
DOI 10.1073/pnas.2116122119
PMID 36252029
PMC PMC9618038
MeSH Amoeba* / genetics Biological Products* / metabolism Dictyostelium* / physiology Polyketide Synthases / genetics Polyketide Synthases / metabolism Polyketides* / metabolism
IF 9.412
Cellular slime molds G90426