A Balancing Act for Taxol Precursor Pathways in E. coli

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Science  01 Oct 2010:
Vol. 330, Issue 6000, pp. 44-45
DOI: 10.1126/science.1195014

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Taxol (paclitaxel) is a widely used cancer drug that was first isolated from the bark of the Pacific yew tree, Taxus brevifolia. In 1991, during early stages of its clinical use, 130 kg of Taxol were extracted from 1000 tons of bark, which required cutting down more than 500,000 mature Pacific yew trees (1). Fortunately, Taxol is presently made by less destructive methods, either through chemical conversion of a related molecule derived from needles of the more prevalent European yew, T. baccata (2), or from cultured plant cells (3). Nonetheless, both these plant-based processes are difficult, and this valuable drug remains expensive. On page 70 of this issue, Ajikumar et al. (4) have made progress toward making Taxol in Escherichia coli, biotechnology's workhorse bacterium, in substantial quantities by balancing several enzymatic pathways to make its complex multicyclic core (see the figure).