title: Enhanced biosynthetic gene expressions and production of ganoderic acids in static liquid culture of Ganoderma lucidum under phenobarbital induction.
abstract: Static liquid culture of Ganoderma lucidum, a traditional Chinese medicinal mushroom, is a proven technology for producing ganoderic acids, which are secondary metabolites that possess antitumor properties. In this work, the addition of phenobarbital, a P450 inducer, was used to enhance the production of total and individual ganoderic acids in a two-stage cultivation involving a period of initial shake flask culture followed by static liquid culture of G. lucidum. The dosage and time of phenobarbital induction were critical for the enhanced production of ganoderic acids. The addition of 100 muM (final concentration) phenobarbital on day 5 after the shake flask culture was converted to the static liquid culture was found to be optimal, resulting in a maximal amount of total ganoderic acids of 41.4 +/- 0.6 mg/g cell dry weight and increases in the levels of ganoderic acid-Mk, -T, -S, and -Me in the treated cells by 47%, 28%, 36%, and 64%, respectively. Meanwhile, the accumulation of lanosterol, a key intermediate, was found to decrease and transcriptions of three key genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase, squalene synthase, and lanosterol synthase in the triterpene biosynthetic pathway were up-regulated under phenobarbital induction. This work demonstrated a useful strategy for the enhanced production of ganoderic acids by G. lucidum.
authors.affiliation: Molecular Biochemical Engineering Group, Key Laboratory of Microbial Metabolism (Ministry of Education), School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Shanghai, 200240, China.
authors.forename: Cui-Xia
authors.initials: CX
authors.lastname: Liang
authors.forename: Ying-Bo
authors.initials: YB
authors.lastname: Li
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Xu
authors.forename: Jia-Le
authors.initials: JL
authors.lastname: Wang
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Miao
authors.forename: Ya-Jie
authors.initials: YJ
authors.lastname: Tang
authors.forename: Tingyue
authors.initials: T
authors.lastname: Gu
authors.forename: Jian-Jiang
authors.initials: JJ
authors.lastname: Zhong
mesh_terms: D004365:Drugs, Chinese Herbal; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D020940:Reishi / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development
chemical_list: D004365:Drugs, Chinese Herbal; D007810:Lanosterol; D010634:Phenobarbital