Construction of an Escherichia coli cell factory to synthesize taxadien-5α-ol, the key precursor of anti-cancer drug paclitaxel

Abstract

•	We report a recombinant Escherichia coli BL21(DE3) strain for de novo production of taxadien-5α-ol, the key precursor of paclitaxel.
•	Through screening of key enzymes and the fermentation condition optimization, the final production of total oxygenated taxanes was raised up to 27 mg L−1 in 50-mL flask cultivation, of which the yield of taxadien-5α-ol was 7.0 mg L−1, representing approximately a 12-fold and 23-fold improvements, respectively.
•	It is believed that the strategy used in this study will guide in the synthesis of terpenoids.

Keywords

Oxygenated taxanes / Metabolic engineering / Taxadiene-5α-hydroxylase / Fusion protein / Mevalonate pathway / Paclitaxel / Escherichia coli

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Funding

National Key Research and Development Program of China(2019YFA0905000)

National Natural Science Foundation of China(21922804)

Program of Shanghai Academic Research Leader(21XD1400800)

Fundamental Research Funds for Central Universities of the Central South University(22221818014)