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Application of Multiple Strategies to Improve the Production of the Potential Cancer Drug 4-Acetylantroquinonol B (4-AAQB) by the Rare Fungus Antrodia cinnamomea

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Abstract

4-Acetylantroquinonol B (4-AAQB) was identified in the rare fungus Antrodia cinnamomea and has been proven to be a potential therapeutic agent for cancer treatment. But the extraction of 4-AAQB from the fruit body led to a low yield and limited its further application in the pharmaceutical field. In this work, 4-AAQB production was enhanced in the submerged fermentation by the combination of exogenous additives, surfactants with the in situ extractive fermentation. 4-Methylbenzoic acid was proven to be an efficient additive for the accumulation of 4-AAQB by Antrodia cinnamomea, while 2% (w/v) Tween-80 added on the first day as surfactant and 30% (w/v) oleic acid added on the sixteenth day as extractant were the most available couples for 4-AAQB production in the in situ extractive fermentation. The combination of these multiple strategies resulted in the yield of 4-AAQB to 17.27 mg/g dry cell weight with a titer of 140 mg/L, which was the highest titer of 4-AAQB reported so far. It showed that the combination of these strategies had a significant promotion on 4-AAQB production by A. cinnamomea, which laid a good foundation for its large-scale production and also provided a viable method for the cultivation of other rare fungi.

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Funding

This research was financially supported by the National Key Research Program (2016YFD0400601, 2017YFB03069043), the Hong Kong, Macao and Taiwan Scientific and Technological Cooperation Projects (2015DFT30050), and National Natural Science Foundation of China (21978019, 21978020).

Author information

Authors and Affiliations

  1. Beijing Bioprocess Key Laboratory, State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, People’s Republic of China

    Huan Liu, Hao Xing, Yuhan Jin, Jie Liu, Li Deng & Fang Wang

  2. Department of Applied Science, National Taitung University, Taitung, Taiwan

    Yew-Min Tzeng

Authors
  1. Huan Liu
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  2. Hao Xing
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  3. Yuhan Jin
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  4. Jie Liu
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  5. Yew-Min Tzeng
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  6. Li Deng
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  7. Fang Wang
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Contributions

Huan Liu and Li Deng conceived the topic and designed the study. Huan Liu: data curation, investigation, methodology, writing original draft; Hao Xing, Yuhan Jin, and Jie Liu: data curation, investigation, methodology; Yew-Min Tzeng, Li Deng, and Fang Wang: writing—review and editing, supervision, funding acquisition, conceptualization, project administration.

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Correspondence to Li Deng.

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Highlights

• 4-MBA was proven to be an efficient exogenous additive for 4-AAQB production.

• The in situ extraction method was applied in 4-AAQB production by A. cinnamomea.

• The addition of surfactants was proven to be beneficial for 4-AAQB production.

• Combining these multiple strategies resulted in 17.27 mg/g 4-AAQB produced.

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Liu, H., Xing, H., Jin, Y. et al. Application of Multiple Strategies to Improve the Production of the Potential Cancer Drug 4-Acetylantroquinonol B (4-AAQB) by the Rare Fungus Antrodia cinnamomea. Appl Biochem Biotechnol 194, 2720–2730 (2022). https://doi.org/10.1007/s12010-022-03811-0

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