4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-12879-y

Keywords

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Funding

  1. National Key R&D Program of China [2018YFA0900600]
  2. Strategic Priority Research Program Molecular mechanism of Plant Growth and Development of CAS [XDB27020202]
  3. National Natural Science Foundation of China [31670099]
  4. Key Research Program of the Chinese Academy of Science [XDPB0400, KFZD-SW-215]
  5. Natural Science Foundation of Shanghai Municipal Science and Technology Committee [17ZR1435000]
  6. Construction of the Registry and Database of Bioparts for Synthetic Biology of the Chinese Academy of Science [ZSYS-016]
  7. International Partnership Program of Chinese Academy of Science [153D31KYSB20170121]
  8. National Key Laboratory of Plant Molecular Genetics, SIPPE, CAS

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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-5 alpha-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-5 alpha-ol, the committed taxol intermediates, at 56.6 mu g g(-1) FW and 1.3 mu g 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.

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