Ganoderic acid (GA), an important secondary metabolite of Ganoderma lucidum, exhibited many significant pharmacological activities. In this study, the biosynthetic mechanism of GAs was investigated by comparing metabolites and transcriptome dynamics during liquid superficial‐static culture (LSSC) and submerged culture (SC). LSSC was a better method to produce GA because thirteen GAs were identified from mycelia by UPLC‐QTOF‐MS, and the content of all GAs was higher in LSSC than in SC. Ergosterol was accumulated during the SC process in G. lucidum. Transcriptome dynamics analysis revealed CYP5150L8 was the key gene regulating lanosterol flux into GA biosynthesis. Other sixteen CYP450 genes were significantly higher expressed during the culture time in LSSC and could be potential candidate genes associated with the biosynthesis of different GAs. In addition, six of the ten expressed genes in ergosterol biosynthetic pathway shown upregulated at some time points in SC. These results not only provide a fundamental information of the key genes in ergosterol and GA biosynthetic pathway, but also provide directions for future elucidating the regulatory mechanisms of GAs in G. lucidum and enabling us to promote the development and utilization of LSSC at the industrial level.

中文翻译：

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转录组动力学和代谢物分析揭示灵芝液体浅层静态培养过程中灵芝酸生物合成的候选基因和调控机制

灵芝酸（GA），一个重要的次级代谢产物灵芝，表现出许多显著的药理活性。在这项研究中，通过比较液体浅层静态培养（LSSC）和水下培养（SC）期间的代谢物和转录组动力学，研究了GA的生物合成机理。LSSC是产生GA的更好方法，因为通过UPLC-QTOF-MS从菌丝体中鉴定出13种GA，并且LSSC中所有GA的含量均高于SC。麦角甾醇在超灵芝中的SC过程中积累。转录组动力学分析显示CYP5150L8是调节羊毛甾醇向GA生物合成通量的关键基因。其他16种CYP450基因在LSSC中的培养期间表达明显较高，并且可能是与不同​​GAs的生物合成相关的潜在候选基因。此外，在麦角固醇生物合成途径中的十个表达基因中有六个在SC中的某些时间点表达上调。这些结果不仅提供了麦角固醇和GA生物合成途径中关键基因的基本信息，而且为今后阐明灵芝中GA的调控机制提供了指导，并使我们能够在工业水平上促进LSSC的开发和利用。 。