The medicinal mushroom Sanghuangporus vaninii produces valuable bioactive compounds, but yields are low in artificial culture. While co-culture with microbes can elicit production, the regulatory potential of native endophytic fungi - which share an evolutionary history with their host - remains largely unexplored. In this study, we report for the first time a co-culture system between S. vaninii and its endophytic fungus Fusarium solani MF20 to enhance the production of medicinal metabolites and elucidate the underlying mechanisms. Co-culture with F. solani MF20 dramatically increased the yields of total flavonoids (9.38-fold), terpenoids (3.18-fold), and crude polysaccharides (4.87-fold) in S. vaninii. Integrated omics analyses revealed that the endophytic interaction induced global metabolic change in the host. Early signaling events, such as a controlled oxidative stress response, Ca2+ influx, extracellular ATP accumulation, and enhanced membrane permeability, were associated with the redirection of cellular resources from primary growth toward chemical defense. Key biosynthetic pathways, such as terpenoid backbone and flavonoid synthesis, were transcriptionally up-regulated, directly corroborated by the massive accumulation of bioactive compounds including the triterpene pachymic acid and complex modified flavonoids. Central carbon metabolism was reshaped, with activation of the pentose phosphate pathway potentially supplying NADPH for biosynthesis. This work demonstrates that a native endophytic fungus can act as a powerful biotic elicitor to unlock the metabolic potential of its medicinal fungal host. The co-culture strategy activates a stress-mediated defense response that reprograms primary and secondary metabolism, leading to overproduction of pharmaceutically relevant compounds. Beyond providing insights into fungal-fungal symbiotic interactions, this study validates endophyte-host co-culture as an effective and sustainable bioprocess technology for enhancing the production of high-value metabolites from medicinal fungal resources.
Ma et al. (Sat,) studied this question.