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Ganoderic acids (GAs), a kind of highly oxygenated lanostane-type triterpenoids, are important bioactive constituents of the famous medicinal mushroom Ganoderma lucidum. They have received wide attention in recent years due to extraordinarily pharmacological functions. Submerged fermentation of G. lucidum is viewed as a promising technology for pro...
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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...
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... It has been used in Asia to improve health and treat various diseases for over 2000 years (Bishop et al., 2015;Hsu and Cheng, 2018). G. lucidum has diverse biological activities including immunomodulation, anticancer, antiaging, and anti-inflammatory effects (Xu et al., 2010b;Ahmad et al., 2022). Owing to its nutritional and medicinal properties, G. lucidum has received widespread attention from academic and industrial communities in recent years due to its nutritional and medicinal properties. ...
Ganoderic acids (GAs) are major functional components of Ganoderma lucidum. The study aimed to breed a new G. lucidum strain with increased contents of individual GAs. Two mating-compatible monokaryotic strains, G. 260125 and G. 260124, were successfully isolated from the dikaryotic G. lucidum CGMCC 5.0026 via protoplast formation and regeneration. The Vitreoscilla hemoglobin gene (vgb) and squalene synthase gene (sqs) were overexpressed in the monokaryotic G. 260124 and G. 260125 strain, respectively. Mating between the G. 260124 strain overexpressing vgb and the G. 260125 strain overexpressing sqs resulted in the formation of the new hybrid dikaryotic G. lucidum strain sqs-vgb. The maximum contents of ganoderic acid (GA)-T, GA-Me, and GA-P in the fruiting body of the mated sqs-vgb strain were 23.1, 15.3, and 39.8 μg/g dry weight (DW), respectively, 2.23-, 1.75-, and 2.69-fold greater than those in G. lucidum 5.0026. The squalene and lanosterol contents increased 2.35- and 1.75-fold, respectively, in the fruiting body of the mated sqs-vgb strain compared with those in the G. lucidum 5.0026. In addition, the maximum expression levels of the sqs and lanosterol synthase gene (ls) were increased 3.23- and 2.13-fold, respectively, in the mated sqs-vgb strain. In summary, we developed a new G. lucidum strain with higher contents of individual GAs in the fruiting body by integrating genetic engineering and mono–mono crossing.
... Ganoderma lucidum is an important edible and medicinal fungus belonging to the family Polyporaceae and genus Ganoderma. Ganoderma lucidum has high nutritional value and is rich in various components such as polysaccharides, total triterpenes, proteins, amino acids, alkaloids, adenine, etc. [1]. Among them, Ganoderma lucidum polysaccharides and triterpenes are the main bioactive substances used to evaluate the value of Ganoderma lucidum. ...
Edible fungi have certain photo-sensitivity during the mushroom emergence stage, but there have been few relevant studies on the responses of Ganoderma lucidum to different light irradiation conditions. Ganoderma lucidum were planted in an environmentally controllable mushroom room with different light supply modes that were, respectively, continuous white light (CK), red light (R), green light (G), blue light (B), and intermittent red light (R-), green light (G-), and blue light (B-), with a total light intensity of 15 μmol·m−2·s−1 and a light/dark (L/D) period of 12 h/12 h for each treatment. The interval in intermittent light treatments was 30 min. The optimal light supply mode suitable for the growth of Ganoderma lucidum was explored by analyzing the characteristics, nutritional quality, and extracellular enzyme activity in mushrooms exposed to different light treatments. The results showed that red light (whether in continuous or intermittent supply modes) inhibited the fruiting body differentiation of Ganoderma lucidum, showing delayed differentiation or complete undifferentiation. The highest stipe length and pileus diameter of fruiting bodies were detected under G- treatment, which were, respectively, increased by 71.3% and 3.2% relative to the control. The highest weight of fruiting bodies was detected under G treatment, which was significantly increased by 21.4% compared to the control (p < 0.05). Intermittent light mode seemed to be more conducive to the size development of the fruiting body, while continuous light mode was beneficial for increasing the weight. The highest contents of crude protein and total triterpenes in pileus were detected under G treatment (significantly 14.9% and 28.1% higher than the control, respectively), while that of the crude polysaccharide was detected under G- treatment (significantly 35.7% higher than the control) (p < 0.05). The highest activities of extracellular enzymes such as cellulase, hemicellulase, laccase, lignin peroxidase, and amylase were detected in fruiting bodies subjected to G treatment, which were significantly increased by 11.9%~30.7% in the pileus and 9.5%~44.5% in the stipe. Green light might increase the weight and nutrient accumulation in the pileus of Ganoderma lucidum via up-regulating the extracellular enzyme activities. This study provides an effective light supply strategy for regulating the light environment in the industrial production of Ganoderma lucidum.
... By optimizing the fermentation process, it is possible to significantly improve the production of GAs. Factors that affect liquid fermentation include the screening of G. lucidum strains, the composition of culture media [65], pH levels, dissolved oxygen, temperature, and agitation rate [66]. ...
... Currently, many researchers have initiated genetic transformation studies on G. lucidum. In 2012, using the electroporation method, researchers successfully transferred the GUS and GFP reporter genes driven by the G. lucidum GDP promoter into the protoplasts, with the bialaphos resistance gene as the selection marker [66]. Subsequently, the researchers used the PEGmediated method to transfer the GUS reporter gene into the protoplasts, with the hygromycin resistance gene as the selection marker, at a transformation frequency of about 5-6 transformants/107 protoplasts [63]. ...
Ganoderma lucidum is a precious fungus, particularly valued for its dual use as both medicine and food. Ganoderic acids (GAs), the distinctive triterpenoids found in the Ganoderma genus, exhibit a wide range of pharmacological activities. However, the limited resources of GAs restrict their clinic usage and drug discovery. In this review, we presented a comprehensive summary focusing on the diverse structures and pharmacological activity of GAs in G. lucidum. Additionally, we discussed the latest advancements in the elucidation of GA biosynthesis, as well as the progress in heterosynthesis and liquid fermentation methods aimed at further increasing GA production. Furthermore, we summarized the omics data, genetic transformation system, and cultivation techniques of G. lucidum, described as medicinal model fungi. The understanding of Ganoderic acids chemodiversity and biosynthesis in medicinal model fungi Ganoderma lucidum will provide important insights into the exploration and utilization of natural products in medicinal fungi.
Supplementary Information
The online version contains supplementary material available at 10.1186/s13020-024-00922-0.
... Their ability to inhibit tumor invasion and metastasis makes them promising candidates for novel anticancer therapies. Additionally, ganoderic acids exhibit hepatoprotective properties, protecting the liver from damage caused by various toxins and oxidative stress (12,14). Studies have also revealed their anti-inflammatory effects, suggesting potential benefits in addressing different inflammatory disorders (15). ...
Introduction
The fruiting body of Ganoderma lucidum has been believed to possess a wide range of therapeutic effects. There are two main methods for artificial cultivation of G. lucidum to produce the fruiting body, namely wood log cultivation and substitute cultivation. The impact of cultivation substrates on the composition of bioactive compounds remains largely unexplored. This study aims to compare the antioxidant activities and triterpenoid profiles of the fruiting bodies of G. lucidum that cultivated through wood log cultivation (WGL) and substitute cultivation (SGL) methods.
Methods
The antioxidant activities, including the DPPH radical scavenging, hydroxyl radical scavenging, superoxide radical scavenging, and total antioxidant activities, were assessed in both WGL and SGL samples. Furthermore, the UHPLC-Q-Orbitrap-MS technique was employed to compare their phytochemical profiles, with a specific emphasis on triterpenoid constituents.
Results and discussion
It was found that WGL samples exhibited significantly higher total triterpenoid content, DPPH radical scavenging activity, and total antioxidant activity. Furthermore, an untargeted metabolomics approach employing UHPLC-Q-Orbitrap-MS tentatively identified a total of 96 triterpenoids. Distinguishingly different triterpenoid profiles between the two types of G. lucidum samples were revealed via the utilization of principal component analysis (PCA) and hierarchical cluster analysis (HCA). Specifically, 17 triterpenoids showed significant differences. Of these triterpenoids, 6 compounds, such as ganosporelactone B, ganoderol A, ganoderic acid A, ganoderic acid alpha, were significantly higher in SGL samples; 11 compounds, such as lucidenic acid A, lucidenic acid D1, lucidenic acid F, lucidenic acid G, lucidenic acid J, ganoderic acid E, and ganoderic acid O, were significantly higher in WGL samples. These findings expand our knowledge regarding the impact of cultivation substrate on the antioxidant activities and triterpenoid profiles of G. lucidum, and offer practical implications for its cultivation.
... 10 Ganoderma contains highly oxygenated lanostane-type triterpenoids, such as ganoderic acids Me and T, which possess potent antitumor activity. 11 More than 400 compounds have been extracted and identified from Ganoderma species and more than 150 Ganoderma terpenoids have been reported. Various types of ganoderic acids from Ganoderma, such as GA-A, GA-C2, GA-D, GA-DM, ganodermanotriol, ganoderiol F, and lactones, have medicinal properties. ...
Mycochemical properties and bioactivities of Ganoderma resinaceum and Serpula similis remain unexplored. The present study assessed antioxidant, cytotoxicity, and cell migration abilities of Ganoderma and Serpula extracts,
followed by their phytochemical analyses. The MTT assay was conducted to determine the cytotoxicity along with the cell
migration studies in human cancer cell lines. The antioxidant profiles were evaluated through DPPH and FRAP assays. Furthermore, LC–MS/MS analysis was performed to elucidate the phytochemicals responsible for anticancer and antioxidant
activities. Significant concentration-dependent cytotoxicities of 12.7% and 13.7% were observed against HCT 116 cell lines
at 1% and 5% concentrations of the G. resinaceum extract, respectively. Similarly, significant concentration-dependent cytotoxicities of 6.7% and 25.5% were observed at 1% and 5% concentrations of the S. similis extract, respectively. The extracts
of G. resinaceum and S. similis both shows better anti-migration potential in lung cancer cells. Both extracts demonstrated
good scavenging activity on DPPH and ferric ion free radicals. LC–MS analysis revealed 11 compounds from S. similis and
15 compounds from G. resinaceum fruiting bodies. Compounds such as terpenoids, alkaloids, cytotoxic peptides, and other
metabolites were identified as major components in both extracts. These extracts exhibited cytotoxic activity against HCT
116 cancer cells, along with moderate antioxidant activity. This implies that the extracts might be used as bioactive natural
sources in the pharmaceutical and food industries.
... Triterpenes play essential roles in immune regulation and other biological activities in humans. Ganoderic acids (GAs) are critical bioactive constituents of the medicinal mushroom Ganoderma lucidum (Komoda et al., 1989;Xu et al., 2010). ...
Animals living in high‐altitude environments, such as the Tibetan Plateau, must face harsh environmental conditions (e.g., hypoxia, cold, and strong UV radiation). These animals' physiological adaptations (e.g., increased red cell production and turnover rate) might also be associated with the gut microbial response. Bilirubin is a component of red blood cell turnover or destruction and is excreted into the intestine and reduced to urobilinoids and/or urobilinogen by gut bacteria. Here, we found that the feces of macaques living in high‐altitude regions look significantly browner (with a high concentration of stercobilin, a component from urobilinoids) than those living in low‐altitude regions. We also found that gut microbes involved in urobilinogen reduction (e.g., beta‐glucuronidase) were enriched in the high‐altitude mammal population compared to the low‐altitude population. Moreover, the spatial–temporal change in gut microbial function was more profound in the low‐altitude macaques than in the high‐altitude population, which might be attributed to profound changes in food resources in the low‐altitude regions. Therefore, we conclude that a high‐altitude environment's stress influences living animals and their symbiotic microbiota.
... Therefore, it is necessary to establish an unambiguous triterpenoid HPLC fingerprint profile for the identification and quality control of G. lucidum mycelium. Here, we isolated nineteen lanostane triterpenes, including five new compounds 1-5 and fourteen known compounds, namely, GA-U1 (6), ganorbiformin C (7), GA-P (8), GA-Q (9), GA-T (10), GA-TS (11), GA-S (12), GA-R (13), GA-Me (14), GmA-S (15), GmA-T-O (16), GA-Mf (17), GmA-P2 (18), and GA-Y (19), from the mycelium of G. lucidum YK-01. Their structures were identified via matching with the published literature [10][11][12][13][14] and spectroscopic data ( 1 H, 13 C NMR, DEPT, HSQC, HMBC, and mass spectrometry). ...
... The absolute ethanol (Fisher Chemical, purity 98%) and glacial acetic acid (PanReac AppliChem, purity 99.8%) were HPLC-grade. The cultivation media including glucose (Dongxiao, Zhucheng, China) [15,16], sucrose (Taiwan Sugar Corporation, Kaohsiung, Taiwan), soy peptone (Organotechnie, La Courneuve, France), malt extract (Stbio media, New Taipei City, Taiwan), yeast extract (Guangxi Yipinxian Biotechnology Co., Ltd., Guangxi, China), and potassium phosphate (Lianyungang Hengsheng Food Additive Co., Ltd., Lianyungang, China) were food-grade. MEA (malt extract agar) was purchased from Merck (Darmstadt, Germany), and PDA was purchased from Difco (Becton Dickinson & Co., Sparks, MD, USA). ...
... The cultivation media and conditions and the harvest timing for the mycelium of G. lucidum may change the relative abundance and pattern of its triterpenes [16]. In addition, a mycelium collected from a liquid fermentation flask will show a lower triterpenoid content than one collected from a static container [16]. ...
(1) Background: Ganoderic acids (GAs) are specific triterpenes of Ganoderma lucidum. The HPLC fingerprint profile of GAs of the fruiting body is well known, but their mycelial fingerprinting remains unclear. (2) Methods: An ethanol extract of the mycelium of G. lucidum (YK-01) was further purified via preparative HPLC. The triterpenoid compositions for four strains of G. lucidum and one strain of G. formosanum (purple lingzhi) were analyzed using HPLC. (3) Results: Nineteen lanostane triterpenes, including five new triterpenes, GA-TP (1), ganodermic acid Jc (GmA-Jc) (2), GmA-Jd (3), GA-TQ1 (4), and ganoderal B1 (5), and fourteen known triterpenes 6–19 were isolated from the ethanol extract. Their structures were identified by mass and extensive NMR spectroscopy. A green chemical HPLC analytical method was developed using ethanol and acetic acid as a mobile phase, and all isolated compounds can be well separated. These triterpenes comprise a unique HPLC chromatograph of the G. lucidum mycelium. All four G. lucidum strains showed the same HPLC chromatographic pattern, whereas G. formosanum displayed a different pattern. Quantitation methods for ganoderic acid T (10) and S (12) were also validated. (4) Conclusions: The triterpenoid HPLC analytical method can be used to identify the G. lucidum species and to determine the contents of GA-T and GA-S.
... The cultivation media and conditions, and the harvest timing for the mycelium of G. lucidum may change the relative abundance and the pattern of its triterpenes [20]. Besides, the mycelium collected from a liquid fermentation flask shows a lower triterpenoid content than that of the collected from a static container [20]. ...
... The cultivation media and conditions, and the harvest timing for the mycelium of G. lucidum may change the relative abundance and the pattern of its triterpenes [20]. Besides, the mycelium collected from a liquid fermentation flask shows a lower triterpenoid content than that of the collected from a static container [20]. Therefore we used the static cultivation method. ...
(1) Background: ganoderic acids (GAs) are specific triterpenes of Ganoderma lucidum. The HPLC fingerprint profile of GAs of the fruiting body has been well-known, but the mycelial fingerprinting remains unclear. (2) Methods: the ethanol extract of the mycelium of G. lucidum (YK-01) was further purified by preparative HPLC. The HPLC spectra for four strains of G. lucidum and one strain of G. formosanum (purple lingzhi) were investigated. (3) Results: nineteen lanostane triterpenes, including five new triterpenes, GA-TP (1), ganodermic acid Jc (GmA-Jc) (2), GmA-Jd (3), GA-TQ1 (4), and ganoderal B1 (5), and fourteen known triterpenes 6-19 were isolated from the ethanol extract. A green chemical HPLC analytical method was developed by using ethanol and acetic acid as mobile phase. These triterpenes comprise of a unique HPLC triterpenoid spectral pattern of G. lucidum mycelium. All four G. lucidum strains showed the same HPLC spectral pattern, whereas G. formosanum displayed a different pattern. Quantitation methods for ganoderic acid T (10) and S (12) were also validated. (4) Conclusions: the triterpenoid HPLC analytical method can be used to identify G. lucidum species, and to determine the contents of GA-T and GA-S.
... Numerous data have been confirmed the potential of G. lucidum as a chemopreventive or chemo-therapeutic agent (Saltarelli et al. 2019). This species possesses a number of pharmacological characteristics, and therefore, they are observed to have analgesic, anti-allergenic, anti-cholesterolemic, anti-diabetic, antihypertensive, anti-inflammatory, anti-mutagenic, antioxidant, antiproliferative, anti-viral (anti-HIV), cardioprotective, chemopreventive, hepatoprotective, immuno-modulating, and renoprotective among others (Kabir et al. 1988;Lakshmi et al. 2003;Zjawiony 2004;Paterson 2006;Ajith and Janardhanan 2007;Shi et al. 2008;Chen and Huang 2010;Xu et al. 2010;De Silva et al. 2012b;Rajasekaran and Kalaimagal 2012;Walton 2014;Luo et al. 2015a, b;Rašeta 2016;Rašeta et al. 2017;Rašeta et al. 2020a;Saltarelli et al. 2019;Wang et al. 2020;Chun et al. 2021;Ermoshin et al. 2022;Karaman et al. 2022). ...
Ganoderma adspersum (Schulzer) Donk; Ganoderma applanatum (Pers.) Pat.; Ganoderma lucidum (Curtis) P. Karst.; Ganoderma resinaceum Boud. - GANODERMATACEAE
Yusufjon Gafforov, Aisha Umar, Soumya Ghosh, Michal Tomšovský, Mustafa Yamaç, Milena Rašeta, Manzura Yarasheva, Wan Abd Al Qadr Imad Wan-Mohtar et Sylvie Rapior.
Ganoderma adspersum (Schulzer) Donk; Ganoderma applanatum (Pers.) Pat.; Ganoderma lucidum (Curtis) P. Karst.; Ganoderma resinaceum Boud. - GANODERMATACEAE. Pages 1135-1169. doi:10.1007/978-3-031-23031-8_111 ; hal-04373752v1 ; hal-04385086v1
... In general, triterpenoids are biosynthesized from the universal triterpenoid compound precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), which are largely produced via mevalonate/isoprenoid (MVA) pathway in the cytoplasm. Then, IPP and DMAPP are catalyzed by farnesyl pyrophosphate synthase (FPS) to generate FPP, which is further catalyzed into squalene in the present of squalene synthase (SQS) [3][4][5][6]. Finally, the precursor of steroids and saponins, lanosterol are produced under the effect of squalene 2,3-epoxidase (SO) and lanosterol synthase (LS). ...
Background: Triterpenoids have shown a wide range of biological activities including antitumor and antiviral effects. Typically, triterpenes are synthesized through the mevalonate pathway and are extracted from natural plants and fungi. In this work, triterpenoids, ganoderic acids (GAs) were discovered to be produced via biotransformation of a diterpene, 15,16-dihydrotanshinone I (DHT) in the liquid cultured Ganoderma sessile mycelium.
Results: Firstly, the biotransformation products, two rare GAs were isolated and purified by column chromatography , and characterized using HR-ESI-MS spectrometry and NMR spectrometry. The two compounds were Lanosta-7,9(11),24-trien-15α,22,β-diacetoxy-3β-hydroxy-26-oic acid (LTHA) and Lanosta-7,9(11),24-trien-15α,22,β-diacetoxy-3β-carbonyl-26-oic acid (LTCA). Then, transcriptome and proteome technologies were employed to measure the expression of mRNA and protein, which further confirmed that triterpenoid GAs could be transformed from exog-enous diterpenoid DHT. At the molecular level, we proposed a hypothesis of the mechanism by which DHT converted to GAs in G. sessile mycelium, and the possible genes involved in biotransformation were verified by RT-qPCR.
Conclusions: Two rare GAs were obtained and characterized. A biosynthetic pathway of GAs from DHT was proposed. Although the synthetic route was not confirmed, this study provided important insights into omics resources and candidate genes for studying the biotransformation of diterpenes into triterpenes.
