Transcriptome dynamics and metabolite analysis revealed the candidate genes and regulatory mechanism of ganoderic acid biosynthesis during liquid superficial-static culture of Ganoderma lucidum.

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.