Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi

Molecules. 2016 Oct 20;21(10):1395. doi: 10.3390/molecules21101395.


Triterpene acids (TAs) are the major bioactive constituents in the medicinal fungus Ganoderma lingzhi. However, fermentative production of TAs has not been optimized for commercial use, and whether the TAs isolated from G. lingzhi submerged culture mycelia possess antitumor activity needs to be further proven. In this study, enhanced TA yield and productivity were attained with G. lingzhi using response surface methodology. The interactions of three variables were studied using a Box-Benhnken design, namely initial pH, dissolved oxygen (DO) and fermentation temperature. The optimum conditions were an initial pH of 5.9, 20.0% DO and 28.6 °C. These conditions resulted in a TA yield of 308.1 mg/L in a 5-L stirred bioreactor. Furthermore, the optimized conditions were then successfully scaled up to a production scale of 200 L, and maximum TA production and productivity of 295.3 mg/L and 49.2 mg/L/day were achieved, which represented 80.9% and 111.5% increases, respectively, compared with the non-optimized conditions. Additionally, the triterpene acid extract (TAE) from G. lingzhi mycelia was found to be cytotoxic to the SMMC-7721 and SW620 cell lines in vitro, and the TAE exhibited dose-dependent antitumor activity against the solid tumor sarcoma 180 in vivo. Chemical analysis revealed that the key active triterpene compounds, ganoderic acid T and ganoderic acid Me, predominated in the extract.

Keywords: Ganoderma lingzhi; antitumor activity; medicinal fungi; response surface methodology; submerged batch fermentation; triterpene acids.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Bioreactors / microbiology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Fermentation
  • Ganoderma / chemistry
  • Ganoderma / growth & development*
  • Humans
  • Lanosterol / administration & dosage
  • Lanosterol / analogs & derivatives
  • Lanosterol / metabolism
  • Lanosterol / pharmacology
  • Mice
  • Mycelium / chemistry
  • Mycelium / growth & development
  • Sarcoma 180 / drug therapy*
  • Triterpenes / administration & dosage*
  • Triterpenes / chemistry
  • Triterpenes / metabolism*
  • Triterpenes / pharmacology
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Triterpenes
  • ganoderic acid
  • ganoderic acid T
  • Lanosterol