Isolation, structural identification, and characterization of a mutagen from Fusarium moniliforme

Strains of Fusarium moniliforme produce a variety of toxins, including several uncharacterized mutagens that act directly in the Ames assay using Salmonella typhimurium, strain TA 100. The Ames assay was used to monitor isolation of the direct-acting mutagens from the F. moniliforme culture extracts. Seven strains were tested, of which strains F07 and F84 contained the highest levels of direct-acting mutagens. Extracts of strain F84 were fractionated on a silica gel column, eluted with methanol-chloroform (1:9). This fraction was then separated on a reverse-phase, C-18 column with 50% methanol in water as eluant and further purified by TLC. One compound was isolated and given the trivial name fusarin X (FX). Its structure was determined from its UV (lambda max 357 nm), 500-MHz NMR, and mass spectra, and those of its diacetate, to be the 1-hydroxy analog of the previously characterized fusarin C. FX was present in culture extracts of strains F07 and F84 at 83 and 8 micrograms/g, respectively, which was proportional to their relative mutagenicities. It was not detected in the other strains tested. Since exposure of FX most likely occurs in cooked corn, its thermal stability was measured; it, like FC, decomposes at 100 degrees C, especially at high pH. Again, in common with FC, it was decomposed by GSH. The possible role of these Fusarium metabolites in the etiology of human cancers has still to be resolved.