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Enhanced biosynthetic gene expressions and production of ganoderic acids in static liquid culture of Ganoderma lucidum under phenobarbital induction

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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 μM (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.

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Acknowledgments

Financial support from the National Natural Science Foundation of China (NSFC Project No. 20776084, No. 30821005), the National High Technology R&D Program (863 Project No. 2007AA021506), Shanghai Science & Technology Commission (Project No. 08DZ1971900), and the Shanghai Leading Academic Discipline Project (Project Nos. B203 and B505) is gratefully acknowledged. We also thank the reviewers for their time and helpful comments.

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Authors and Affiliations

  1. 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

    Cui-Xia Liang, Jun-Wei Xu, Jia-Le Wang, Xiao-Ling Miao & Jian-Jiang Zhong

  2. State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China

    Ying-Bo Li

  3. Key Laboratory of Fermentation Engineering (Ministry of Education) and Hubei Provincial Key Laboratory of Industrial Microbiology, College of Bioengineering, Hubei University of Technology, Wuhan, 430068, China

    Ya-Jie Tang

  4. Department of Chemical and Biomolecular Engineering, Ohio University, Athens, OH, 45701, USA

    Tingyue Gu

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  1. Cui-Xia Liang
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  2. Ying-Bo Li
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Correspondence to Jian-Jiang Zhong.

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Liang, CX., Li, YB., Xu, JW. et al. Enhanced biosynthetic gene expressions and production of ganoderic acids in static liquid culture of Ganoderma lucidum under phenobarbital induction. Appl Microbiol Biotechnol 86, 1367–1374 (2010). https://doi.org/10.1007/s00253-009-2415-8

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  • DOI: https://doi.org/10.1007/s00253-009-2415-8

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