• Logo
  • SBMUJournals

Impact of Rifampin Induction on the Fermentation Production of Ganoderic Acids by Medicinal Mushroom Ganoderma lucidum

Fahimeh Nojoki, Ashrafalsadat Hatamian-Zarmi, Mohammad Mir-Drikvand, Bahman Ebrahimi-Hosseinzadeh, Zahra-begom Mokhtari-Hosseini, Saeed Kalantari-Dehaghi, Maryam Esmaeilifar




Backgrounds and Objectives: Ganoderic acids are the most valuable secondary metabolites in Ganoderma lucidum traditional medicinal mushrooms, which have shown antitumor properties in many studies. However, application of ganoderic acids is limited due to low yield production. Recently, it was shown that static liquid culture could be a proven technology for producing ganoderic acids in Ganoderma lucidum, and that applying elicitors could be a potential strategy to improve their production.


Materials and Methods: In this work, the effect of rifampin, a cyto-chromes P450 inducer, on production of ganoderic acids was studied, and Response Surface Methodology was applied to optimize the elicitor induction. Then total ganoderic acid in the harvested mycelia was extracted and its absorbency was measured.


Results and Conclusion: The results showed an increase in the concen-tration of ganoderic acid in all samples. Moreover, optimum concentration and induction time of rifampin were obtained. The proposed model predicted the maximum ganoderic acid production as 18.6 mg g-1 in which the optimal concentration and time induction obtained were 100 μM and day 9, respectively. This work demonstrated a useful method for the enhanced production of ganoderic acids by Ganoderma lucidum


Cancer, Elicitor, Ganoderic acids, Ganoderma lucidum, Rifampin


Tung N, Trang T, Cuong T. Cytotoxic triterpenoids from the fruiting bodies of Ganoderma lucidum. Nat Prod Sci. 2014; 20: 7-12.

Wachtel S, Tomlinson B, Benzie I. Ganoderma lucidum ('Lingzhi') a Chinese medicinal mushroom: Biomarker responses in a controlled human supplementation study. Br J Nutr. 2004; 91: 263-269.

Ruan W, Popovich G. Evidence of bioactivity from Ganoderma lucidum triterpenoids in cultured cell models. Saponins: Properties, Applications and Health Benefits. 2012; 145-156.

Ruan W, Lim A, Huang L, Popovich D. Extraction optimisation and isolation of triterpenoids from Ganoderma lucidum and their effect on human carcinoma cell growth. Nat Prod Res. 2014; 28: 2264-2272.

Wu G, Guo J, Bao L. Anti-cancer properties of triterpenoids isolated from Ganoderma lucidum-a review. Expert Opin Inv Drug. 2013; 22: 981-992.

Bae W, Kim Y, Lee J. Bioactive substances from Ganoderma lucidum. Korean J Microbiol Biotechnol. 2005; 33: 75-83.

Pan D, Wang L, Chen C, Teng B, Wang C, Xu Z. Structure characterization of a novel neutral polysaccharide isolated from Ganoderma lucidum fruiting bodies. Food Chem. 2012; 135: 1097-1103.

Min B, Lee H, Bae K, Gao J, Nakamura N, Hattori M. Antitumor activity of cultured mycelia of Ganoderma lucidum. Nat Prod Sci. 2002; 8: 52-54.

Xu P, Ding Z, Qian Z. Improved production of mycelial biomass and ganoderic acid by submerged culture of Ganoderma lucidum SB97 using complex media. Enzyme Microb Technol. 2008; 42: 325-331.

Liu GQ, Wang X L, Han WJ, Lin QL. Improving the fermentation production of the individual key triterpene ganoderic acid me by the medicinal fungus Ganoderma lucidum in submerged culture. Molecules. 2012; 17: 12575-12586.

Zhou JS, Ji SL, Ren MF, He YL, Jing XR, Xu JW. Enhanced accumulation of individual ganoderic acids in a submerged culture of Ganoderma lucidum by the overexpression of squalene synthase gene. Biochem Eng J. 2014; 90:178-183.

Zhao ZZ, Yin RH, Chen HP, Feng T, Li ZH, Dong ZJ. Two new triterpenoids from fruiting bodies of fungus Ganoderma lucidum. J Asian Nat Prod Res. 2015; 15: 117-123.

Zhang J, Zhong JJ, Geng A. Improvement of ganoderic acid production by fermentation of Ganoderma lucidum with cellulase as an elicitor. Process Biochem. 2014; 49: 1580-1586.

Liang CX, Li YB, Xu JW, Wang JL, Miao XL, Tang YJ. Enhanced biosynthetic gene expressions and production of ganoderic acids in static liquid culture of Ganoderma lucidum under phenobarbital induction. Appl Microbiol Biotechnol. 2010; 86: 1367-1374.

Howard P, Twycross R, Grove G, Charlesworth S, Mihalyo M, Wilcock A. Rifampin. J Pain Symptom Manage. 2015; 50: 891-895.

Guengerich FP, Role of cytochrome P450 in drug-drug interactions. Adv Pharmacol. 1997; 43:7-35.

He M, Zhang S, Jiao Y, Lin X, Huang J, Chen C. Effects and mechanisms of rifampin on hepatotoxicity of acetaminophen in mice. Food Chem Toxicol. 2012; 3142-3149.

Cao J, Sun W, Pan Y, Chen S. High-Producers of Polygalacturonase Selected From Mutants Resistant to Rifampin in Alkalophilic Bacillus sp. NTT33. Enzyme Microb Technol. 2000; 27: 545-548.

Liu GQ, Zhao Y, Wang XL, Zhu CY, Response surface methodology for optimization of polysaccharides extraction by mild alkaline hydrolysis from fruiting body of medicinal mushroom, Ganoderma lucidum. J Med Plants Res. 2011; 5: 2064-2070.

20 Fang Q, Zhong JJ. Two-stage culture process for improved production of ganoderic acid by liquid fermentation of higher fungus Ganoderma lucidum. Biotechnol Prog. 2002; 18: 51-54.

Karlson AG, Ulrich JA. Stability of rifampin in dimethylsulfoxide. Appl Microbiol. 1969; 18: 692-693.

Xu YN, Xia XX, Zhong JJ. Induction of ganoderic acid biosynthesis by Mn2+ in static liquid cultivation of Ganoderma lucidum. Biotechnol Bioeng. 2014; 111: 2358-2365.

Zhang J, Zhong JJ, Geng A. Improvement of ganoderic acid production by fermentation of Ganoderma lucidum with cellulase as an elicitor. Process Biochem. 2014; 49: 1580-1586.

Liu Q, Xiao HX, Wang XL, Zhao Y, Zhang YG, Ren GP. Stimulated Production of Triterpenoids of Ganoderma lucidum by an Ether Extract from the Medicinal Insect, Catharsius molossus, and Identification of the Key Stimulating Active Components. Appl Biochem Biotechnol. 2011; 165: 87-97.

Zhu LW, Zhong JJ, Tang YJ. Significance of fungal elicitors on the production of ganoderic acid and Ganoderma polysaccharides by the submerged culture of medicinal mushroom Ganoderma lucidum. Proc Biochem. 2008; 43: 1359-1370.

Ren A, Qin L, Shi L, Dong X, Mu DS, Li YX. Methyl jasmonate induces ganoderic acid biosynthesis in the basidiomycetous fungus Ganoderma lucidum. Bioresource Technol. 2010; 101: 6785-6790.

Heydarian MS, Hatamian AS, Amoabediny Gh, Yazdian F, Doryab A, Synergistic Effect of Elicitors in Enhancement of Ganoderic Acid Production: Optimization and Gene Expression Studies. Appl Food Biotechnol. 2015; 2: 57-62.

Zhu LW, Tang YJ, Significance of protein elicitor isolated from tuber melanosporum on the production of ganoderic acid and Ganoderma polysaccharides during the fermentation of Ganoderma lucidum. Bioproc Biosyst Eng. 2010; 33: 999-1005.

DOI: https://doi.org/10.22037/afb.v3i2.10797


  • There are currently no refbacks.