| Summary: | <i>Cordyceps chanhua</i> is an important cordycipitoid mushroom widely used in Asia and beyond. Beauvericin (BEA), one of the bioactive compounds of <i>C. chanhua</i>, has attracted much attention because of its medicinal value and food safety risk. In order to clear up the relationship between oxidative stress and BEA synthesis, we investigated the impact of H<sub>2</sub>O<sub>2</sub>-induced oxidative stress on the secondary metabolism of <i>C. chanhua</i> using untargeted metabolomics and a transcript profiling approach. Metabolic profiling of <i>C. chanhua</i> mycelia found that in total, 73 differential metabolites were identified, including organic acids, phospholipids, and non-ribosomal peptides (NRPs), especially the content of BEA, increasing 13-fold under oxidative stress treatment. Combining transcriptomic and metabolomic analyses, we found that the genes and metabolites associated with the NRP metabolism, especially the BEA biosynthesis, were highly significantly enriched under H<sub>2</sub>O<sub>2</sub>-induced stress, which indicated that the BEA metabolism might be positive in the resistance of <i>C. chanhua</i> to oxidative stress. These results not only aid in better understanding of the resistance mechanisms of <i>C. chanhua</i> against oxidative stress but also might be helpful for molecular breeding of <i>C. chanhua</i> with low BEA content.
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