title: Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi.
abstract: Triterpene acids (TAs) are the major bioactive constituents in the medicinal fungusGanoderma lingzhi. However, fermentative production of TAs has not been optimized for commercial use, and whether the TAs isolated fromG. lingzhisubmerged culture mycelia possess antitumor activity needs to be further proven. In this study, enhanced TA yield and productivity were attained withG. lingzhiusing 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) fromG. lingzhimycelia 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.
authors: Key Laboratory of Cultivation and Protection for Non-Wood Forest Trees, Ministry of Education, Central South University of Forestry and Technology, Changsha 410004, China. cathy8311@163.com.|Hunan Provincial Key Laboratory for Control of Forest Diseases and Pests, College of Life Science and Technology, Central South University of Forestry & Technology, Changsha 410004, China. cathy8311@163.com.
authors: Xiao-Ling
authors: XL
authors: Wang
authors: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China. qinxinhuzhu@tom.com.
authors: Zhong-Yang
authors: ZY
authors: Ding
authors: Key Laboratory of Cultivation and Protection for Non-Wood Forest Trees, Ministry of Education, Central South University of Forestry and Technology, Changsha 410004, China. gaoliuedu@csuft.edu.cn.|Hunan Provincial Key Laboratory for Control of Forest Diseases and Pests, College of Life Science and Technology, Central South University of Forestry & Technology, Changsha 410004, China. gaoliuedu@csuft.edu.cn.
authors: Gao-Qiang
authors: GQ
authors: Liu
authors: College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China. yanzhaocsuft@sina.com.
authors: Hailong
authors: H
authors: Yang
authors: Key Laboratory of Cultivation and Protection for Non-Wood Forest Trees, Ministry of Education, Central South University of Forestry and Technology, Changsha 410004, China. gyzhouedu@aliyun.com.|Hunan Provincial Key Laboratory for Control of Forest Diseases and Pests, College of Life Science and Technology, Central South University of Forestry & Technology, Changsha 410004, China. gyzhouedu@aliyun.com.
authors: Guo-Ying
authors: GY
authors: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019149:Bioreactors / Q000382:microbiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005285:Fermentation; D032902:Ganoderma / Q000737:chemistry / Q000254:growth & development*; D006801:Humans; D007810:Lanosterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D025282:Mycelium / Q000737:chemistry / Q000254:growth & development; D012510:Sarcoma 180 / Q000188:drug therapy*; D014315:Triterpenes / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes; C556862:ganoderic acid; C550530:ganoderic acid T; D007810:Lanosterol
keywords: Ganoderma lingzhi; antitumor activity; medicinal fungi; response surface methodology; submerged batch fermentation; triterpene acids