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

Abstract

Highlights 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