The regulatory and transcriptional landscape associated with triterpenoid and lipid metabolisms by the bHLH-zip transcription factor SREBP in the medicinal fungus Ganoderma lingzhi

Abstract Ganoderic acids (GAs) are well recognized as important pharmacological components of the medicinal species belonging to the basidiomycete genus Ganoderma. However, transcription factors directly regulating the expression of GA biosynthesis genes remain poorly understood. Here, the genome of Ganoderma lingzhi was de novo sequenced. Using DAP-seq, we identified putative targets of the transcription factor SREBP, including the genes of triterpenoid synthesis and lipid metabolism. Interactions between SREBP and the targets were verified by EMSA. RNA-seq showed that SREBP targets, mevalonate kinase and 3-hydroxy-3-methylglutaryl CoA synthetase in mevalonate pathway, sterol isomerase and lanosterol 14-demethylase in ergosterol biosynthesis, were significantly upregulated in the SREBP overexpression strain. In addition, 3 targets involved in glycerophospholipid/glycerolipid metabolism were upregulated. Then, the contents of mevalonic acid, lanosterol, ergosterol and 13 different GAs as well as a variety of lipids were significantly increased in this strain. Furthermore, the effects of SREBP overexpression on triterpenoid and lipid metabolisms were recovered when OE::SREBP strain were treated with exogenous fatostatin, a specific inhibitor of SREBP. Taken together, our genome-wide study clarified the role of SREBP in triterpenoid and lipid metabolisms of G. lingzhi.