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.
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bHLH-zip转录因子SREBP调节药用真菌灵芝中的三萜和脂质代谢
DOI：
10.1038/s42003-022-04154-6
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发表时间：
2023-01-03
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
灵芝酸是担子菌属灵芝属药用植物的重要药理成分。然而，直接调控GA生物合成基因表达的转录因子仍然知之甚少。在这里，灵芝的基因组被重新测序。通过DNA亲和纯化测序，我们鉴定了转录因子固醇调节元件结合蛋白(SREBP)的可能靶点，包括三萜类合成和脂类代谢的基因。电泳迁移率凝胶漂移分析证实了SREBP与靶分子之间的相互作用。RNA-SEQ结果表明，SREBP基因在SREBP过表达(OE：：SREBP)菌株中显著上调。SREBP靶标甲戊酸途径中的甲戊酸激酶和3-羟基-3-甲基戊二酰辅酶A合成酶，麦角甾醇生物合成中的甾醇异构酶和羊毛甾醇14-脱甲基酶。此外，还上调了与甘油磷脂/甘油脂代谢有关的3个靶点。同时，该菌株的甲戊酸、羊毛甾醇、麦角甾醇和13种不同的GAS以及多种脂类的含量均显著增加。此外，当用SREBP的特异性抑制剂Fate ostatin处理OE：：SREBP菌株时，SREBP过表达对三萜类和脂类代谢的影响得到恢复。综上所述，我们的全基因组研究阐明了SREBP在灵芝三萜类和脂类代谢中的作用。结合基因组学、DAP-seq、RNA-seq、代谢组学和遗传学等方法，确定SREBP是灵芝中调节三萜和脂类代谢的关键转录因子。
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. An integration of genomic, DAP-seq, RNA-seq, metabolomic and genetic approaches identifies SREBP as a key transcription factor regulating triterpenoid and lipid metabolisms in the medicinal fungus Ganoderma lingzhi.
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影响因子：
3.7
作者：
Huang YH;Wu HY;Wu KM;Liu TT;Liou RF;Tsai SF;Shiao MS;Ho LT;Tzean SS;Yang UC
通讯作者：
Yang UC
影响因子：
48
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通讯作者：
Salzberg, Steven L.
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通讯作者：
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影响因子：
5.1
作者：
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通讯作者：
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