CER1 ceramide synthase orthologs mediate FB1 resistance in the fumonisin-producing Fusarium verticillioides and the non-producing F. graminearum

Abstract Molecular mechanisms responsible for self-protection in fumonisin-producing fungi are still barely understood. A role for fumonisin in competition between fungi was proposed, particularly between Fusarium verticillioides and non-producing F. graminearum on maize. Recently, it was shown that the FUM-cluster associated ceramide synthase genes of F. verticilliodes ( FUM17 and FUM18 ) are dispensable for the observed higher fumonisin resistance in F. verticillioides . To test the role of CER1 , we have inactivated this gene in F. verticillioides (in the wild-type, fum1 and fum1 fum17-18 background). Despite the expected redundancy of ceramide synthases, inactivation of CER1 in F. verticillioides lead to inhibition of growth by 80-90% and FB 1 sensitivity at a concentration of only 10 μM. While the slow-growth phenotype could be complemented by expression of both a FvCER1 cDNA and the corresponding F. graminearum CER1 ortholog, this was not the case for the Saccharomyces cerevisiae LAG1 and LAC1 ceramide synthase genes. The F. graminearum CER1 not only complemented the growth defect but even conferred slightly higher FB 1 resistance. Heterologous expression in a sensitive yeast strain revealed that all F. verticillioides and also F. graminearum CER1 , CER2 and CER3 genes confer FB 1 resistance, but CER2 and CER3 only against lower concentrations. However, overexpression of CER2 and CER3 is problematic due to toxicity in yeast leading to variable results. We hypothesize that F. graminearum ancestors may have lost the ability to produce fumonisin, but maintained the self-protection mechanism against sphinganine-analog mycotoxins based on target insensitivity.