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Unexpected Metabolic Versatility in a Combined Fungal Fomannoxin/Vibralactone Biosynthesis

Schwenk, Daniel, Brandt, Philip, Blanchette, Robert A., Nett, Markus, Hoffmeister, Dirk
Journal of natural products 2016 v.79 no.5 pp. 1407-1414
Basidiomycota, bioactive compounds, biosynthesis, carbon, fungi, isoprene, isotope labeling, mass spectrometry, metabolome, nuclear magnetic resonance spectroscopy, stable isotopes
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. ¹³C-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.