Mechanism of Fumonisin Self-Resistance: Fusarium verticillioides Contains Four Fumonisin B 1 -Insensitive-Ceramide Synthases.

Fusarium verticillioides produces fumonisins, which are mycotoxins inhibiting sphingolipid biosynthesis in humans, animals, and other eukaryotes. Fumonisins are presumed virulence factors of plant pathogens, but may also play a role in interactions between competing fungi. We observed higher resistance to added fumonisin B 1 (FB 1 ) in fumonisin-producing Fusarium verticillioides than in nonproducing F. graminearum , and likewise between isolates of Aspergillus and Alternaria differing in production of sphinganine-analog toxins. It has been reported that in F. verticillioides , ceramide synthase encoded in the fumonisin biosynthetic gene cluster is responsible for self-resistance. We reinvestigated the role of FUM17 and FUM18 by generating a double mutant strain in a fum1 background. Nearly unchanged resistance to added FB 1 was observed compared to the parental fum1 strain. A recently developed fumonisin-sensitive baker's yeast strain allowed for the testing of candidate ceramide synthases by heterologous expression. The overexpression of the yeast LAC1 gene, but not LAG1 , increased fumonisin resistance. High-level resistance was conferred by FUM18 , but not by FUM17 . Likewise, strong resistance to FB 1 was caused by overexpression of the presumed F. verticillioides "housekeeping" ceramide synthases CER1 , CER2 , and CER3 , located outside the fumonisin cluster, indicating that F. verticillioides possesses a redundant set of insensitive targets as a self-resistance mechanism.