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Chloroplastic metabolic engineering coupled with isoprenoid pool enhancement for committed taxanes biosynthesis in Nicotiana benthamiana

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  • Jianhua Li

    (Chinese Academy of Sciences)

  • Ishmael Mutanda

    (Chinese Academy of Sciences)

  • Kaibo Wang

    (Chinese Academy of Sciences
    Henan University)

  • Lei Yang

    (Shanghai Chenshan Botanical Garden)

  • Jiawei Wang

    (Chinese Academy of Sciences)

  • Yong Wang

    (Chinese Academy of Sciences)

Abstract

Production of the anticancer drug Taxol and its precursors in heterologous hosts is more sustainable than extraction from tissues of yew trees or chemical synthesis. Although attempts to engineer the Taxol pathway in microbes have made significant progress, challenges such as functional expression of plant P450 enzymes remain to be addressed. Here, we introduce taxadiene synthase, taxadiene-5α-hydroxylase, and cytochrome P450 reductase in a high biomass plant Nicotiana benthamiana. Using a chloroplastic compartmentalized metabolic engineering strategy, combined with enhancement of isoprenoid precursors, we show that the engineered plants can produce taxadiene and taxadiene-5α-ol, the committed taxol intermediates, at 56.6 μg g−1 FW and 1.3 μg g−1 FW, respectively. In addition to the tools and strategies reported here, this study highlights the potential of Nicotiana spp. as an alternative platform for Taxol production.

Suggested Citation

  • Jianhua Li & Ishmael Mutanda & Kaibo Wang & Lei Yang & Jiawei Wang & Yong Wang, 2019. "Chloroplastic metabolic engineering coupled with isoprenoid pool enhancement for committed taxanes biosynthesis in Nicotiana benthamiana," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12879-y
    DOI: 10.1038/s41467-019-12879-y
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    Cited by:

    1. Chengshuai Yang & Yan Wang & Zhen Su & Lunyi Xiong & Pingping Wang & Wen Lei & Xing Yan & Dawei Ma & Guoping Zhao & Zhihua Zhou, 2024. "Biosynthesis of the highly oxygenated tetracyclic core skeleton of Taxol," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Jack Chun-Ting Liu & Ricardo De La Peña & Christian Tocol & Elizabeth S. Sattely, 2024. "Reconstitution of early paclitaxel biosynthetic network," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Hao-Tian Wang & Zi-Long Wang & Kuan Chen & Ming-Ju Yao & Meng Zhang & Rong-Shen Wang & Jia-He Zhang & Hans Ågren & Fu-Dong Li & Junhao Li & Xue Qiao & Min Ye, 2023. "Insights into the missing apiosylation step in flavonoid apiosides biosynthesis of Leguminosae plants," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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