Different polyketide folding modes converge to an identical molecular architecture

Metabolic diversity is being studied intensively by evolutionary biologists, but so far there has been no comparison of biosynthetic pathways leading to a particular secondary metabolite in both prokaryotes and eukaryotes. We have detected the bioactive anthraquinone chrysophanol, which serves as a chemical defense in diverse eukaryotic organisms, in a bacterial Nocardia strain, thereby permitting the first comparative biosynthetic study. Two basic modes of folding a polyketide chain to fused-ring aromatic structures have so far been described(1): mode F (referring to fungi) and mode S (from Streptomyces). We have demonstrated that in eukaryotes (fungi, higher plants and insects), chrysophanol is formed via folding mode F. In actinomycetes, by contrast, the cyclization follows mode S. Thus, chrysophanol is the first polyketide synthase product that is built up by more than one polyketide folding mode.