2. Academic Validation
  3. The bHLH-zip transcription factor SREBP regulates triterpenoid and lipid metabolisms in the medicinal fungus Ganoderma lingzhi

The bHLH-zip transcription factor SREBP regulates triterpenoid and lipid metabolisms in the medicinal fungus Ganoderma lingzhi

  • Commun Biol. 2023 Jan 3;6(1):1. doi: 10.1038/s42003-022-04154-6.
Yong-Nan Liu 1 2 3,  Feng-Yuan Wu 1 2 3,  Ren-Yuan Tian 1 2 3,  Yi-Xin Shi 1 2 3,  Zi-Qi Xu 1 2 3,  Ji-Ye Liu 1 2 3,  Jia Huang 1 2 3,  Fei-Fei Xue 1 2 3,  Bi-Yang Liu 1 2 3,  Gao-Qiang Liu 4 5 6
Affiliations

Affiliations

  • 1 Hunan Provincial Key Laboratory of Forestry Biotechnology, Central South University of Forestry & Technology, Changsha, Hunan, 410004, China.
  • 2 International Cooperation Base of Science and Technology Innovation on Forest Resource Biotechnology of Hunan Province, Central South University of Forestry & Technology, Changsha, Hunan, 410004, China.
  • 3 Microbial Variety Creation Center, Yuelushan Laboratory of Seed Industry, Changsha, 410004, China.
  • 4 Hunan Provincial Key Laboratory of Forestry Biotechnology, Central South University of Forestry & Technology, Changsha, Hunan, 410004, China. [email protected].
  • 5 International Cooperation Base of Science and Technology Innovation on Forest Resource Biotechnology of Hunan Province, Central South University of Forestry & Technology, Changsha, Hunan, 410004, China. [email protected].
  • 6 Microbial Variety Creation Center, Yuelushan Laboratory of Seed Industry, Changsha, 410004, China. [email protected].
PMID: 36596887 DOI: 10.1038/s42003-022-04154-6
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 is de novo sequenced. Using DNA affinity purification sequencing, we identify putative targets of the transcription factor sterol regulatory element-binding protein (SREBP), including the genes of triterpenoid synthesis and lipid metabolism. Interactions between SREBP and the targets are verified by electrophoretic mobility gel shift assay. RNA-seq shows that SREBP targets, mevalonate kinase and 3-hydroxy-3-methylglutaryl coenzyme A synthetase in mevalonate pathway, sterol isomerase and lanosterol 14-demethylase in ergosterol biosynthesis, are significantly upregulated in the SREBP overexpression (OE::SREBP) strain. In addition, 3 targets involved in glycerophospholipid/glycerolipid metabolism are upregulated. Then, the contents of mevalonic acid, lanosterol, ergosterol and 13 different GAs as well as a variety of lipids are significantly increased in this strain. Furthermore, the effects of SREBP overexpression on triterpenoid and lipid metabolisms are recovered when OE::SREBP strain are treated with exogenous fatostatin, a specific inhibitor of SREBP. Taken together, our genome-wide study clarify the role of SREBP in triterpenoid and lipid metabolisms of G. lingzhi.

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