Phosphatidic acid directly activates mTOR and then regulates SREBP to promote ganoderic acid biosynthesis under heat stress in Ganoderma lingzhi

Ganoderic acids (GAs), a class of secondary metabolites produced by the traditional medicinal mushroom Ganoderma, are a group of triterpenoids with superior biological activities. Heat stress (HS) is one of the most important environmental abiotic stresses. Understanding how organisms sense temperature and integrate this information into their metabolism is important for determining how organisms adapt to climate change and for applying this knowledge to breeding. We previously reported that HS induced GA biosynthesis, and phospholipase D (PLD)-mediated phosphatidic acid (PA) was involved in HS-induced GA biosynthesis. We screened a proteome to identify the PA-binding proteins in G. lingzhi. We reported that PA directly interacted with mTOR and positively correlated with the ability of mTOR to promote GA biosynthesis under HS. The PA-activated mTOR pathway promoted the processing of the transcription factor sterol regulatory element-binding protein (SREBP) under HS, which directly activated GA biosynthesis. Our results suggest that SREBP is an intermediate of the PLD-mediated PA-interacting protein mTOR in HS-induced GA biosynthesis. Our report established the link between PLD-mediated PA production and the activation of mTOR and SREBP in the HS response and HS-induced secondary metabolism in filamentous fungi. A study on how organisms sense temperature and integrate this into their metabolism suggests that PLD-mediated PA directly activates mTOR and regulates SREBP to promote the transcription of target genes and GA biosynthesis under heat in G. lingzhi.