Overproduction of Taxadiene in Engineered Escherichia coli

Taxol (Paclitaxel) is one of the blockbuster anticancer drugs in the clinic with excellent activity against a range of cancers. Recent developments in metabolic engineering and synthetic biology have allowed overproduction of terpenoid based on microbial fermentation rather than the time consuming and low yield plant-based production, resulting in remarkable breakthroughs in the production of complex natural products such as taxadiene, the precursor of taxol. Here, we constructed a rationally designed recombinant E. coli strain that could be engineered for high-level production of taxadiene. Base on the instruction of in vitro reconstitution of mevalonate (MVA) pathway, the production of two universal 5-carbon isoprenoid precursors, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) were optimized, together with the heterologous taxadiene forming pathway carrying geranyl diphosphate synthase (GGPPS) and taxadiene synthase (TS) of different origin, taxadiene production in E. coli was significantly increased at the shake-flask scale. This work could be regarded as a novel platform for engineering of other terpenoid synthesis from mevalonate pathway. Successful overproduction of taxadiene has encouraged the hope that the terpenoid metabolic pathway can be rationally engineered for enhanced productivity with limited engineering procedure.