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

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 furt...

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Autores principales: Wang, Xiao-Ling, Ding, Zhong-Yang, Liu, Gao-Qiang, Yang, Hailong, Zhou, Guo-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273529/
https://www.ncbi.nlm.nih.gov/pubmed/27775633
http://dx.doi.org/10.3390/molecules21101395
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author Wang, Xiao-Ling
Ding, Zhong-Yang
Liu, Gao-Qiang
Yang, Hailong
Zhou, Guo-Ying
author_facet Wang, Xiao-Ling
Ding, Zhong-Yang
Liu, Gao-Qiang
Yang, Hailong
Zhou, Guo-Ying
author_sort Wang, Xiao-Ling
collection PubMed
description 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.
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spelling pubmed-62735292018-12-28 Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi Wang, Xiao-Ling Ding, Zhong-Yang Liu, Gao-Qiang Yang, Hailong Zhou, Guo-Ying Molecules Article 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. MDPI 2016-10-20 /pmc/articles/PMC6273529/ /pubmed/27775633 http://dx.doi.org/10.3390/molecules21101395 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Xiao-Ling
Ding, Zhong-Yang
Liu, Gao-Qiang
Yang, Hailong
Zhou, Guo-Ying
Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi
title Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi
title_full Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi
title_fullStr Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi
title_full_unstemmed Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi
title_short Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi
title_sort improved production and antitumor properties of triterpene acids from submerged culture of ganoderma lingzhi
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273529/
https://www.ncbi.nlm.nih.gov/pubmed/27775633
http://dx.doi.org/10.3390/molecules21101395
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