Abstract
Ganoderic acids (GAs) are a type of highly oxygenated lanostane-type triterpenoids that are responsible for the pharmacological activities of Ganoderma lucidum. They have been investigated for their biological activities, including antibacterial, antiviral, antitumor, anti-HIV-1, antioxidation, and cholesterol reduction functions. Inducer supplementation is viewed as a promising technology for the production of GAs. This study found that supplementation with sodium acetate (4 mM) significantly increased the GAs content of fruiting bodies by 28.63% compared to the control. In order to explore the mechanism of ganoderic acid accumulation, the transcriptional responses of key GAs biosynthetic genes, including the acetyl coenzyme A synthase gene, and the expression levels of genes involved in calcineurin signaling and acetyl-CoA content have been analyzed. The results showed that the expression of three key GAs biosynthetic genes (hmgs, fps, and sqs) were significantly up-regulated. Analysis indicated that the acetate ion increased the expression of genes related to acetic acid assimilation and increased GAs biosynthesis, thereby resulting in the accumulation of GAs. Further investigation of the expression levels of genes involved in calcineurin signaling revealed that Na+ supplementation and the consequent exchange of Na+/Ca2+ induced GAs biosynthesis. Overall, this study indicates a feasible new approach of utilizing sodium acetate elicitation for the enhanced production of valuable GAs content in G. lucidum, and also provided the primary mechanism of GAs accumulation.
Highlights
Ganoderma lucidum, known as ‘the mushroom of immortality’ and ‘the symbol of traditional Chinese medicine’, is one of the best-known medicinal macrofungi in the world [1,2]
Ganoderic acids (GAs) are synthesized via the mevalonate pathway (MVA), wherein acetyl-CoA is converted to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) through a series of chemical reactions, and further to mevalonate (MVA) to isopentenyl pyrophosphate (IPP) to farnesyl diphosphate (FPP) to squalene, and to lanosterol [7,8,9]
3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) [10], farnesyl pyrophosphate synthase (FPS) [11], squalene synthase (SQS) [12], and oxidosqualene cyclase (OSC) [13] have been identified as key enzymes involved in triterpenoid biosynthesis, and their enhanced expression is found to promote the accumulation of GAs [14,15]
Summary
Known as ‘the mushroom of immortality’ and ‘the symbol of traditional Chinese medicine’, is one of the best-known medicinal macrofungi in the world [1,2]. 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) [10], farnesyl pyrophosphate synthase (FPS) [11], squalene synthase (SQS) [12], and oxidosqualene cyclase (OSC) [13] have been identified as key enzymes involved in triterpenoid biosynthesis, and their enhanced expression is found to promote the accumulation of GAs [14,15]. The content of GAs in the fruiting body was significantly higher than that in the mycelia It remains unclear whether the methods reported to increase GAs production in the mycelia stage could be applied toward the fruiting body stage. The present study aimed to enhance GAs accumulation in the fruiting body of G. lucidum using sodium acetate as an inducer. To explore the underlying mechanisms responsible for its accumulation, the transcripts of genes encoding key enzymes in the GAs biosynthetic pathway, acs and those of genes in the calcineurin signal pathway, were assayed
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