ASPERGILLUS SPORULATION AND MYCOTOXIN PRODUCTION BOTH REQUIRE INACTIVATION OF THE FADA G-ALPHA PROTEIN-DEPENDENT SIGNALING PATHWAY

The filamentous fungus Aspergillus nidulans contains a cluster of 25 g enes that encode enzymes required to synthesize a toxic and carcinogen ic secondary metabolite called sterigmatocystin (ST), a precursor of t he better known fungal toxin aflatoxin (AF), One ST Cluster (sfc) gene , aflR, functions as a pathway-specific transcriptional regulator for activation of other genes in the ST pathway. However, the mechanisms c ontrolling activation of aflR and synthesis of ST and AF are not under stood, Here we show that one important level for control of ste gene e xpression requires genes that were first identified as early acting re gulators of asexual sporulation. Specifically, we found that loss-of-f unction mutations in flbA, which encodes a RGS domain protein, or domi nant activating mutations in fadA, which encodes the alpha subunit of a heterotrimeric G protein, block both ST production and asexual sporu lation. Moreover, overexpression of flbA or dominant interfering fadA mutations cause precocious ste gene expression and ST accumulation, as well as unscheduled sporulation, The requirement for flbA in sporulat ion and ST production could Be suppressed by loss-of-function fadA mut ations. The ability of flbA to activate ste gene expression was depend ent upon another early acting developmental regulator, fluG, and AAR, the ste gene-specific transcription factor These results are consisten t with a model in which both asexual sporulation and ST production req uire inactivation of proliferative growth through inhibition of FadA-d ependent signaling, This regulatory mechanism is conserved in AF-produ cing fungi and could therefore provide a means of controlling AF conta mination.