Enhanced Production of Ganoderic Acids and Cytotoxicity of<i>Ganoderma lucidum</i>Using Solid-Medium Culture

You, Bang‐Jau; Lee, Hong‐Zin; Chung, Kwong T.; Lee, Miin-Huey; Huang, Mei-Jung; Tien, Ni; Chan, C; Kuo, Yueh‐Hsiung

doi:10.1271/bbb.120270

Cited by 26 publications

(20 citation statements)

References 47 publications

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“…Extraction and detection of ganoderic acids (GAs) from the fungal mycelium was performed as previously described [17]. Dried mycelium (100 mg) was extracted with methanol, and GAs in supernatant was analyzed by HPLC.…”

Section: Methodsmentioning

confidence: 99%

“…The application of various inducers, such as phenobarbital and methyl jasmonate, has been used to enhance GA production in submerged culture [15], [16]. Our recent studies have revealed that G. lucidum produces large quantity of GAs when cultured on solid-state medium [17]. However, regulation of triterpenoids biosynthesis and its signal transduction remains enigmatic for G. lucidum .…”

Section: Introductionmentioning

confidence: 99%

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A Novel Approach to Enhancing Ganoderic Acid Production by Ganoderma lucidum Using Apoptosis Induction

et al. 2013

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Ganoderma lucidum is one of most widely used herbal medicine and functional food in Asia, and ganoderic acids (GAs) are its active ingredients. Regulation of GA biosynthesis and enhancing GA production are critical to using G. lucidum as a medicine. However, regulation of GA biosynthesis by various signaling remains poorly understood. This study investigated the role of apoptosis signaling on GA biosynthesis and presented a novel approach, namely apoptosis induction, to increasing GA production. Aspirin was able to induce cell apoptosis in G. lucidum, which was identified by terminal deoxynucleotidyl transferase mediated dUPT nick end labeling assay positive staining and a condensed nuclear morphology. The maximum induction of lanosta-7,9(11), 24-trien-3α-01-26-oic acid (ganoderic acid 24, GA24) production and total GA production by aspirin were 2.7-fold and 2.8-fold, respectively, after 1 day. Significantly lower levels of GA 24 and total GAs were obtained after regular fungal culture for 1.5 months. ROS accumulation and phosphorylation of Hog-1 kinase, a putative homolog of MAPK p38 in mammals, occurred after aspirin treatment indicating that both factors may be involved in GA biosynthetic regulation. However, aspirin also reduced expression of the squalene synthase and lanosterol synthase coding genes, suggesting that these genes are not critical for GA induction. To the best of our knowledge, this is the first report showing that GA biosynthesis is linked to fungal apoptosis and provides a new approach to enhancing secondary metabolite production in fungi.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Approach to Enhancing Ganoderic Acid Production by Ganoderma lucidum Using Apoptosis Induction

et al. 2013

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“…Based on previous results, it has been proposed that the biosynthesis of GAs proceeds via the mevalonate/isoprenoid pathway (Zhao et al, 2007). Further studies have indicated that many environmental factors, including exogenous CaCl 2 , phenobarbital, H 2 O 2 and methyl jasmonate affect the production of GAs, and these agents have been used to enhance GA production in submerged cultures (Liang et al, 2010;Ren et al, 2010;You et al, 2012). The results presented in the present study showed that the GA content was decreased in GPx-silenced strains and could be reverted after the addition of exogenous Ca 2+ (Fig.…”

Section: Gpx-regulated Ros Regulated Ga Biosynthesis Via the Ca 2+ Simentioning

confidence: 99%

Functional analysis of the role of glutathione peroxidase (GPx) in the ROS signaling pathway, hyphal branching and the regulation of ganoderic acid biosynthesis in Ganoderma lucidum

Shi

Chen

et al. 2015

Fungal Genetics and Biology

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“…The quantification of GAs in samples of the fungal mycelium was conducted as described in previous studies 18, 54 . GAs were extracted from the fungal mycelium using methanol and then analyzed by HPLC.…”

Section: Methodsmentioning

confidence: 99%

“…For evaluating the gene expression of SQS and LS at the mRNA level, the corresponding DNA fragments were cloned from G. lucidum BCRC 36111 18, 54 , and northern blotting was performed using standard procedures. Trizol reagent (Invitrogen, Carlsbad, CA, USA) was used to extract fungal total RNA per the manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

Induction of apoptosis and ganoderic acid biosynthesis by cAMP signaling in Ganoderma lucidum

You

Tien

Lee

et al. 2017

Sci Rep

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Apoptosis is an essential physiological process that controls many important biological functions. However, apoptosis signaling in relation to secondary metabolite biosynthesis in plants and fungi remains a mystery. The fungus Ganoderma lucidum is a popular herbal medicine worldwide, but the biosynthetic regulation of its active ingredients (ganoderic acids, GAs) is poorly understood. We investigated the role of 3′,5′-cyclic adenosine monophosphate (cAMP) signaling in fungal apoptosis and GA biosynthesis in G. lucidum. Two phosphodiesterase inhibitors (caffeine and 3-isobutyl-1-methylxanthine, IBMX) and an adenylate cyclase activator (sodium fluoride, NaF) were used to increase intracellular cAMP levels. Fungal apoptosis was identified by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and a condensed nuclear morphology. Our results showed that GA production and fungal apoptosis were induced when the mycelium was treated with NaF, caffeine, or cAMP/IBMX. Downregulation of squalene synthase and lanosterol synthase gene expression by cAMP was detected in the presence of these chemicals, which indicates that these two genes are not critical for GA induction. Transcriptome analysis indicated that mitochondria might play an important role in cAMP-induced apoptosis and GA biosynthesis. To the best of our knowledge, this is the first report to reveal that cAMP signaling induces apoptosis and secondary metabolite production in fungi.

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Enhanced Production of Ganoderic Acids and Cytotoxicity ofGanoderma lucidumUsing Solid-Medium Culture

Cited by 26 publications

References 47 publications

A Novel Approach to Enhancing Ganoderic Acid Production by Ganoderma lucidum Using Apoptosis Induction

A Novel Approach to Enhancing Ganoderic Acid Production by Ganoderma lucidum Using Apoptosis Induction

Functional analysis of the role of glutathione peroxidase (GPx) in the ROS signaling pathway, hyphal branching and the regulation of ganoderic acid biosynthesis in Ganoderma lucidum

Induction of apoptosis and ganoderic acid biosynthesis by cAMP signaling in Ganoderma lucidum

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