Fungal biosynthesis of the bibenzoquinone oosporein to evade insect immunity

Oosporein, a red 1,4-bibenzoquinone derivative, was first identified from fungi in the 1960s and exhibits antibiotic, antiviral, antifungal, and insecticidal activities. We report, to our knowledge, for the first time the novel pathway for oosporein biosynthesis in Beauveria bassiana that includes the polyketide synthase oosporein synthase 1 (OpS1) to produce the precursor orsellinic acid for OpS4 hydroxylation and then OpS7 oxidation to benzenetetrol, and the dimerization of the intermediate to oosporein is catalyzed by the catalase OpS5. The gene cluster is regulated by the transcription factor OpS3. We also found that oosporein is required for fungal virulence by inhibiting insect immunity. These results advance the knowledge of quinone biosynthetic machineries and demonstrate that a small molecule contributes to fungus-host interactions.