title: A novel approach to enhancing ganoderic acid production by Ganoderma lucidum using apoptosis induction.
abstract: 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.
authors: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan. bangjau@mail.cmu.edu.tw
authors: Bang-Jau
authors: BJ
authors: You
authors: Miin-Huey
authors: MH
authors: Lee
authors: Ni
authors: N
authors: Tien
authors: Meng-Shiou
authors: MS
authors: Lee
authors: Hui-Chuan
authors: HC
authors: Hsieh
authors: Lin-Hsien
authors: LH
authors: Tseng
authors: Yu-Lin
authors: YL
authors: Chung
authors: Hong-Zin
authors: HZ
authors: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D018533:Biomass; D018929:Cell Culture Techniques / Q000379:methods*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020940:Reishi / Q000166:cytology* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014315:Triterpenes / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014315:Triterpenes; C556862:ganoderic acid; D013186:Farnesyl-Diphosphate Farnesyltransferase; D020928:Mitogen-Activated Protein Kinases; D019751:Intramolecular Transferases; C021924:lanosterol synthase; D001241:Aspirin