Medicinal Plant Research 2025, Vol.15, No.2, 51-61 http://hortherbpublisher.com/index.php/mpr 53 2.3 Importance of triterpenoid content enhancement The efficacy of G. lucidumoften depends on the amount of triterpenoids in it. The higher the content, the more obvious the therapeutic effect. This is not only a laboratory speculation, but also supported by experimental evidence. For example, Ye et al. (2018) found that spraying salicylic acid (SA) during the formation of G. lucidum fruiting bodies can increase the triterpenoid content by 23.32%. This improvement directly leads to the enhancement of pharmacological effects. But the significance is not just "curing diseases". For the market, increasing the triterpenoid content is equivalent to increasing the added value of the product. G. lucidumproducts are not only pharmaceutical raw materials, but also enter the field of functional foods and nutritional supplements. For these products, triterpenoids are like a "selling point", the higher the better. They not only provide basic nutrition, but also enhance immunity, anti-inflammatory, and even help prevent certain chronic diseases (Ahmad et al., 2021b). 3 Genetic Basis of Triterpenoid Biosynthesis 3.1 Key genes involved in triterpenoid pathway In recent years, the identification of key genes in the triterpenoid biosynthesis pathway of G. lucidumhas become a research focus. For example, the cytochrome P450 gene CYP512U6 is considered to be an important gene in the biosynthesis of ganoderic acid (oxidized triterpenoids). Studies have found that the CYP512U6 gene is involved in the synthesis of ganoderic acid, generating new ganoderic acid compounds through hydroxylation, increasing the diversity of triterpenoid compounds produced by G. lucidum(Yang et al., 2018). Due to the difficulty of genetic manipulation of G. lucidumand its slow growth, researchers have achieved heterologous synthesis of ganoderic acid by expressing the cytochrome P450 gene cyp5150l8 in G. lucidumin Saccharomyces cerevisiae to produce anti-tumor ganoderic acid. This provides a new approach for the industrial production of ganoderic acid (Wang et al., 2018). Xu et al. (2022a) first identified the transcription factor GlbHLH5, which can positively regulate the biosynthesis of triterpenes in G. lucidum. In particular, under the induction of methyl jasmonate, GlbHLH5 significantly responded and promoted the expression of key enzyme genes (such as HMGR, SQS and LS), thereby increasing the production of triterpenoids (Figure 1). In addition, genes such as hmgr, hmgs, mvd, fps, sqs and ls are involved in the early stages of triterpenoid synthesis, especially in the mevalonate pathway, which is crucial for the synthesis of triterpenoid precursors (Ye et al., 2018). Figure 1 Schematic of the predicted regulatory effect of GlbHLH5 in Ganoderma triterpenoids biosynthesis. The solid box represents the main pathway (MVA pathway) of Ganoderma triterpenoids. AACT, acetyl-CoA acetyltransferase; HMGS, 3-hydroxy-3-methylglutaryl-CoA synthase; HMGR, 3-hydroxy-3-methylglutaryl-CoA reductase, SQS, squalene synthase; SE, squalene monooxygenase; LS, lanosterol synthase (Adopted from Xu et al., 2022a)
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