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Enhanced production of camptothecin and biological preparation of N 1-acetylkynuramine in Camptotheca acuminata cell suspension cultures

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Abstract

The Camptotheca acuminata cell suspension cultures were established to produce the well-known antitumor monoterpene indole alkaloid camptothecin (CAM). Most CAM was present in the broth of the C. acuminata cell suspension cultures. The CAM production was evidenced to be attenuated when the C. acuminata cell suspension cultures were continuously subcultured and grown under identical axenic conditions. A practical cryopreservation and recovery procedure was established to maintain the C. acuminata cell suspension cultures. Biotic and abiotic elicitors were administrated to the C. acuminata cell suspension cultures to restore and enhance CAM production. Of them, sorbitol, a well-known hyperosmotic stressor, was proven to be the most effective elicitor that stimulates a ∼500-fold increase of CAM production. The committed biosynthetic precursors of CAM, tryptamine and secologanin, were feed to the C. acuminata cell suspension cultures and the CAM production is not remarkably increased. However, N 1-acetylkynuramine (NAK), an important metabolite of kynuramine pathway, was isolated and identified from the cell suspension cultures feeding with tryptamine. The present work provides an efficient method to produce CAM and NAK using the C. acuminata cell suspension cultures. The biotransformation of tryptamine to NAK sheds lights on the biosynthetic formation of the pyrroloquinoline moiety of CAM.

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Authors and Affiliations

  1. Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, People’s Republic of China

    Yun Yang, Xiang Pu, Xixing Qu, Fei Chen, Guolin Zhang & Yinggang Luo

  2. University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China

    Yun Yang, Xiang Pu, Xixing Qu & Fei Chen

  3. College of Science, Sichuan Agricultural University, Ya’an, 625014, People’s Republic of China

    Xiang Pu

  4. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, People’s Republic of China

    Yinggang Luo

Authors
  1. Yun Yang
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  2. Xiang Pu
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  3. Xixing Qu
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  4. Fei Chen
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  5. Guolin Zhang
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  6. Yinggang Luo
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Correspondence to Yinggang Luo.

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Funding

This work was supported in part by the KSCX2-EW-Q-6 and ZHTS-003 projects from the Chinese Academy of Sciences, the Applied and Basic Research Program of Sichuan Province (2015JY0058), and the 21172216 project from the National Natural Science Foundation of China.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Yun Yang and Xiang Pu authors contributed equally to this work.

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Yang, Y., Pu, X., Qu, X. et al. Enhanced production of camptothecin and biological preparation of N 1-acetylkynuramine in Camptotheca acuminata cell suspension cultures. Appl Microbiol Biotechnol 101, 4053–4062 (2017). https://doi.org/10.1007/s00253-017-8153-4

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  • DOI: https://doi.org/10.1007/s00253-017-8153-4

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