title: Induced sclerotium formation exposes new bioactive metabolites from Aspergillus sclerotiicarbonarius.
abstract: Sclerotia are known to be fungal survival structures, and induction of sclerotia may prompt production of otherwise undiscovered metabolites. Aspergillus sclerotiicarbonarius (IBT 28362) was investigated under sclerotium producing conditions, which revealed a highly altered metabolic profile. Four new compounds were isolated from cultivation under sclerotium formation conditions and their structures elucidated using different analytical techniques (HRMS, UV, 1D and 2D NMR). This included sclerolizine, an alkylated and oxidized pyrrolizine, the new emindole analog emindole SC and two new carbonarins; carbonarins I and J. We have identified the three latter as true sclerotial metabolites. All metabolites were tested for antifungal and antiinsectan activity, and sclerolizine and carbonarin I displayed antifungal activity against Candida albicans, while all four showed antiinsectan activity. These results demonstrate induction of sclerotia as an alternative way of triggering otherwise silent biosynthetic pathways in filamentous fungi for the discovery of novel bioactive secondary metabolites.
authors.affiliation: Natural Product Discovery Group, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Lene M
authors.initials: LM
authors.lastname: Petersen
authors.affiliation: Natural Product Discovery Group, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Frisvad
authors.affiliation: Natural Product Discovery Group, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Knudsen
authors.affiliation: Blumenbach Institute of Zoology and Anthropology, Animal Ecology, Georg-August-University of Göttingen, Göttingen, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Rohlfs
authors.affiliation: Department of Chemistry, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Gotfredsen
authors.affiliation: Natural Product Discovery Group, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Larsen
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001230:Aspergillus / Q000737:chemistry* / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011758:Pyrroles / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000935:Antifungal Agents; D003470:Culture Media; D006574:Heterocyclic Compounds, 2-Ring; D011758:Pyrroles; C000604586:sclerolizine