Methyl viologen boosts Erinacine A biosynthesis in Hericium erinaceus fermentation: Multi-omics insights

Erinacine A, a critical secondary metabolite of Hericium erinaceus , has garnered significant interest due to its bioactive properties. This study aimed to investigate the effects of methyl viologen (MV) on the synthesis of Erinacine A during liquid fermentation of Hericium erinaceus , employing a multi-omics approach to elucidate the underlying mechanisms. Our findings demonstrate that the addition of 5 mg/L of MV after four days of fermentation significantly enhanced Erinacine A production, achieving a remarkable yield of 23 mg/g and 414 mg/L, marking the highest yield reported to date. Scanning electron microscopy (SEM) revealed a distinctive wrinkled and collapsed mycelial surface, indicative of stress responses. Moreover, metabolomics and transcriptomics analyses revealed oxidative stress within Hericium erinaceus , characterized by the downregulation of antioxidant-like metabolites and alterations in the oxidoreductase system. MV was found to impact several metabolic pathways, notably those associated with sugars, amino acids, and fatty acids. Comprehensive analysis of the omics data confirmed that MV enhances the expression of the mevalonate pathway and the Eri gene cluster in response to oxidative stress induced by reactive oxygen species (ROS). This process facilitates the conversion of geranylgeranyl pyrophosphate (GGPP) into Erinacine-like substances. This study provides novel insights, demonstrating for the first time that MV can be effectively utilized in the liquid fermentation of Hericium erinaceus to significantly improve the yield of Erinacine A.