Unexpected Metabolic Versatility in a Combined Fungal Fomannoxin/Vibralactone Biosynthesis.
The secondary metabolome of an undescribed stereaceous basidiomycete (BY1) was investigated for bioactive compounds. Along with a known fomannoxin derivative and two known vibralactones, we here describe three new compounds of these natural product families, whose structures were elucidated using 1D and 2D NMR spectroscopy and high-resolution mass spectrometry. The new compound vibralactone S (4) shows a 3,6-substituted oxepin-2(7H)-one ring system, which is unprecedented for the vibralactone/fomannoxin class of compounds. Stable isotope labeling established a biosynthetic route that is dissimilar to the two published cascades of oxepinone formation. Another new compound, the antifungal methyl seco-fomannoxinate (6), features a 2-methylprop-1-enyl ether moiety, which is only rarely observed with natural products. The structure of 6 was confirmed by total synthesis. (13)C-labeling experiments revealed that the unusual 2-methylprop-1-enyl ether residue derives from an isoprene unit. The diversity of BY1's combined fomannoxin/vibralactone metabolism is remarkable in that these compound families, although biosynthetically related, usually occur in different organisms.
Department of Pharmaceutical Microbiology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität , Beutenbergstrasse 11a, 07745 Jena, Germany.
Daniel
D
Schwenk
Department of Pharmaceutical Microbiology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität , Beutenbergstrasse 11a, 07745 Jena, Germany.
Philip
P
Brandt
Plant Pathology, University of Minnesota , 1991 Upper Buford Circle, Saint Paul, Minnesota 55108, United States.
Robert A
RA
Blanchette
Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute , Beutenbergstrasse 11a, 07745 Jena, Germany.|Department of Biochemical and Chemical Engineering, Technical Biology, Technical University Dortmund , Emil-Figge-Strasse 66, 44227 Dortmund, Germany.
Markus
M
Nett
Department of Pharmaceutical Microbiology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität , Beutenbergstrasse 11a, 07745 Jena, Germany.
Dirk
D
Hoffmeister
D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D003883:Arthrodermataceae / Q000187:drug effects; D001232:Aspergillus fumigatus / Q000187:drug effects; D001487:Basidiomycota / Q000737:chemistry*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry; D002176:Candida albicans / Q000187:drug effects; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010408:Penicillium chrysogenum / Q000187:drug effects
D000935:Antifungal Agents; D001572:Benzofurans; D007783:Lactones; C522315:vibralactone; C084141:fomannoxin