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

Jianhua Li, Ishmael Mutanda, Kaibo Wang, Lei Yang, Jiawei Wang and Yong Wang ()
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Jianhua Li: Chinese Academy of Sciences
Ishmael Mutanda: Chinese Academy of Sciences
Kaibo Wang: Chinese Academy of Sciences
Lei Yang: Shanghai Chenshan Botanical Garden
Jiawei Wang: Chinese Academy of Sciences
Yong Wang: Chinese Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12879-y

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