isotrichodermin and 3-acetyldeoxynivalenol

3-Acetyldeoxynivalenol is the major trichothecene produced by the fungus Fusarium culmorum. The first proven tricyclic intermediate in the biosynthesis of 3-acetyldeoxynivalenol has been shown by in vivo studies to be isotrichodermin, a natural metabolite of F. culmorum. Indeed, the feeding of ring-deuterated isotrichodermin resulted in ring-deuterated 3-acetyldeoxynivalenol as shown by NMR studies. In this work, we have shown that the 3-acetyl group of isotrichodermin is mostly lost in its metabolism to 3-acetyldeoxynivalenol. We have shown by two different approaches that the deacetylation occurs at an early step after the first oxygenation step at C-15. Derivatives of isotrichodermin lacking the 3-acetyl such as 3-deacetyl isotrichodermin or 3-oxo-12,13-epoxytrichothec-9-ene are not precursors to 3-acetyldeoxynivalenol. The role of this acetyl exchange mechanism is not clear presently.

Topics: Carbon Radioisotopes; Chromatography, High Pressure Liquid; Deuterium; Fusarium; Magnetic Resonance Spectroscopy; Molecular Structure; Radioisotope Dilution Technique; Trichothecenes

Upon feeding an excess of the substrate isotrichodermin, five tricyclic metabolites accumulated in Fusarium culmorum cultures. These compounds were also identified as transient intermediates of trichothecene biosynthesis by kinetic pulse labeling. Their structures were characterized by spectroscopic techniques (1H NMR, 13C NMR, 2H NMR, and nuclear Overhauser effect difference experiments) as: 1, 15-deacylcalonectrin; 2, calonectrin; 3, 7-hydroxyisotrichodermin; 4, 8-hydroxyisotrichodermin; and 5, 7, hydroxycalonectrin. Four of these metabolites (1-4) were rigorously proven to be biosynthetic precursors to 3-acetyldeoxynivalenol. Indeed, their deuteriated derivatives were shown to be incorporated very efficiently into 3-acetyldeoxynivalenol by 2H-NMR. In addition, our experimental data suggests that the first oxygenation step after isotrichodermin is at C-15, producing 15-deacylcalonectrin.

Topics: Kinetics; Magnetic Resonance Spectroscopy; Molecular Conformation; Oxidation-Reduction; Oxygen; Trichothecenes