Biosynthetic and toxic potential of ergot: Biological activity of ergot alkaloids and genome mining for the identification further potential toxic secondary metabolites

• Applicant: Professor Dr. Hans-Ulrich Humpf
• Subject Area: Organismic Interactions, Chemical Ecology and Microbiomes of Plant Systems ; Food Chemistry
• Term: from 2012 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 227350539

Claviceps purpurea is a plant pathogenic fungus which is well known for the production of toxic ergot alkaloids. Besides this not much is known about the production of other secondary metabolites. In the first funding period two secondary metabolite gene clusters were characterized in detail in C. purpurea. The first cluster with a nonreducing polyketide synthase as key enzyme (PKS4) was identified as the ergochrome gene cluster responsible for the production of pigments. The second identified cluster with a nonribosomal peptide synthetase as key enzyme (NRPS3) shows homology to clusters encoding epipolythiodiketopiperazine (ETP) toxins characterized by a diketopiperazine ring with an internal disulfide-bridge. Unexpectedly, no molecules with the typical ETP structures could be detected. Instead, several intermediates with an unusual nitrogen-sulfur bond were identified. The overexpression of a cytochrome P450 oxidase from the ETP cluster in Leptospaeria revealed new compounds, named clapurines, with the typical ETP structure.Goal of this proposal is (1) the detailed characterization of further new secondary metabolite gene clusters with so far unknown function in C. purpurea using a genome mining approach and the structure elucidation of the biosynthetic endproducts, (2) to elucidate the detailed mechanism for the formation of the newly identified clapurines as well as the metabolites of the ETP-like gene cluster with the unusual N-S moiety, (3) to study the cytotoxicity of all new secondary metabolites of C. purpurea as these metabolites might play a role as food contaminants and (4) to characterize so far unknown pigments produced also under stress conditions and to elucidate their biosynthetic pathway.

• DFG Programme: Research Grants