期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：36
页码：11365-11370
DOI：10.1073/pnas.1503200112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceOosporein, 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. Quinones are widely distributed in nature and exhibit diverse biological or pharmacological activities; however, their biosynthetic machineries are largely unknown. The bibenzoquinone oosporein was first identified from the ascomycete insect pathogen Beauveria bassiana >50 y ago. The toxin can also be produced by different plant pathogenic and endophytic fungi with an array of biological activities. Here, we report the oosporein biosynthetic machinery in fungi, a polyketide synthase (PKS) pathway including seven genes for quinone biosynthesis. The PKS oosporein synthase 1 (OpS1) produces orsellinic acid that is hydroxylated to benzenetriol by the hydroxylase OpS4. The intermediate is oxidized either nonenzymatically to 5,5'-dideoxy-oosporein or enzymatically to benzenetetrol by the putative dioxygenase OpS7. The latter is further dimerized to oosporein by the catalase OpS5. The transcription factor OpS3 regulates intrapathway gene expression. Insect bioassays revealed that oosporein is required for fungal virulence and acts by evading host immunity to facilitate fungal multiplication in insects. These results contribute to the known mechanisms of quinone biosynthesis and the understanding of small molecules deployed by fungi that interact with their hosts.
