Targeted deletion of cc63tf and cc12grf reveals opposing regulation of beauvericin biosynthesis in Cordyceps cicadae.

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Citation abstract

Cordyceps cicadae (C. cicadae), a species widely used in traditional Chinese medicine, belongs to the family Cordycepsaceae (order Hypocreales, class Ascomycota). Its potential as a novel food resource is limited by the high accumulation of beauvericin (BEA), a toxic secondary metabolite. The effects of gene deletion of two transcription factors and one global regulatory factor on beauvericin biosynthesis were investigated. The Δcc63tf mutant exhibited increased BEA accumulation (11.157 mg/kg), whereas Δcc12grf showed markedly reduced BEA accumulation (>90% reduction, 1.005 mg/kg), achieving food-safe thresholds (3 mg/kg). Notably, Δcc57ef impaired fruiting body development. Transcriptome profiling revealed key differentially expressed genes linked to BEA biosynthesis, with qPCR validation suggesting the regulatory roles of CC63TF as a negative and CC12GRF as a positive regulator. These findings provide evidence for regulatory mechanisms associated with BEA biosynthesis in C. cicadae and provide a genetic framework for strain improvement through precision metabolic engineering, enabling safe industrial application in the functional food and nutraceutical sectors.