The FlbC transcription factor contributes to the generation of strain heterogeneity in Fumagillin mycotoxin production in Aspergillus fumigatus

Aspergillus fumigatus shows inter-strain heterogeneity in the repertoire of secondary metabolites such as mycotoxin fumagillin but the mechanism by which this heterogeneity arises in those production is still not understood. Here, we investigates the effect of the flbC gene on fumagillin production in A. fumigatus by introducing flbC deletions into laboratory strains, A1151, A1159, and A1280 from different backgrounds and examines the effect of the flbC gene on inter-strain heterogeneity. We found that, although all three laboratory strains were capable of producing fumagillin, there was heterogeneity in the effects of flbC gene deletion on fumagillin production. This heterogeneity may be dependent on differences in the expression levels of the fma gene family involved in fumagillin production and different levels of transcriptional activation by transcription factors FapR and LaeA. The flbC gene expression level peaks at the same time as peak mycelial growth but shows differential expression level, suggesting that the differences among strains in the range of expression levels are dependent on differences in the upstream expression of flbC. Thus, our findings show that the different interactions between flbC and factors regulating the expression of fumagillin gene cluster are the probable cause for heterogeneity in fumagillin production in the organism.