Cost-effective, large-scale production of oncology drug Taxol (paclitaxel) intermediates could eventually be achieved using engineered Escherichia coli.
Since Taxol was first produced by isolating it from the bark of the Pacific yew tree numerous alternative production methods have been developed. Now researchers have created a process that could lead to more cost-effective production of Taxol precursors and other chemicals.
The research, published in the October 1 edition of Science , details how E coli was used to produce 1g of taxadiene, a precursor of Taxol, per litre of culture. Producing taxadiene at this concentration represents a 1,000-fold increase over earlier synthesis using E coli.
Increases to taxadiene concentration were achieved by dividing the metabolic pathway into two parts: the upstream element that produces isopentenyl pyrophosphate and a downstream terpenoid–forming pathway.
Researchers identified conditions that optimally balance the two parts of the pathway to maximise production of taxadiene while limiting accumulation of indole, an inhibitory compound. Finally, the researchers engineered the next step in Taxol biosynthesis and produced taxadiene-5alpha-ol.
Despite these advances significant work is needed before commercial scale production of Taxol in E coli is a viable alternative to current methods.
"Though this is only a first step, it is a very promising development and certainly supports this approach and its potential”, said Blaine Pfeifer of Tufts University School of Engineering.
Approaches used in the research, notably dividing the pathway into two elements, could have applications in the engineered production of terpenoid natural products.