Structure and biosynthesis of fungal secondary metabolites

Sammanfattning: The root rot pathogen Heterobasidion annosum s.l., i.e. H. abietinum, H. parviporum, H. annosum s.s., H. irregulare and H. occidentale, and the biocontrol fungus Phlebiopsis gigantea were investigated regarding their secondary metabolites. Thirty-three compounds, in total, were identified from H. annosum s.l. by HRMS and NMR, including six new fomannosin related sesquiterpenes (illudolone A and B, illudolactone A and B and deoxyfomannosin A and B), one new fomajorin-type compound and seven previously unreported natural products with fomannoxin related structures. The new fomannosin related compounds were proposed to be intermediates in the biosynthesis of the known phytoxin fomannosin. Fomannoxin is a benzohydrofuran that previously has been suggested to be involved in the pathogenicity of H. annosum s.l. The biosynthesis of fomannoxin was investigated through an isotopic enrichment study utilizing [1-13C]glucose as metabolic tracer. The results showed that fomannoxin is produced by a combination of the MVA pathway and the shikimic acid pathway. The secondary metabolite production of the species within H. annosum s.l. was analyzed by LC-HRMS. Subsequent principal component analysis showed that the samples from the five species grouped in accord with the respective species, preferred host and previously established phylogeny. The biocontrol fungus P. gigantea is used to prevent root rot caused by H. annosum s.l. Its mode of action was studied by investigating the production of secondary metabolites. Five secondary metabolites were isolated and identified by HRMS and NMR, out of which three were new compounds (phlebiopsin A-C), one was a new natural product (methyl-terfestatin A) and one was a known compound (o-orsellinaldehyde). Only o-orsellinaldehyde showed growth inhibiting activity against H. occidentale.