Paclitaxel Production Update

Although a fermentation route to taxadiene is of some interest, “Boosting Taxol Production” is out-of-date in suggesting that this might lead to a breakthrough in the production of paclitaxel (Taxol), which the C&EN article claims “is currently produced by chemically modifying baccatin III, which is isolated from needles of the European yew tree” (C&EN, Oct. 4, page 6). In fact, paclitaxel itself is already produced by an aqueous-based plant cell fermentation (PCF) process.

The story behind Bristol-Myers Squibb’s 2002 decision to discontinue the semisynthetic paclitaxel route and focus solely on the PCF route is detailed in chapter 7 of “Green Chemistry in the Pharmaceutical Industry” (Dunn, P. J. et al., editors. Weinheim: Wiley-VCH, 2010). Using technology licensed from Phyton Biotech GmbH, BMS scientists developed a PCF process using cells cultured from the needles of the Chinese yew tree (Taxus chinensis). Implementation of the PCF process on a commercial scale overcame the many disadvantages of the semisynthetic route, which included the need for large plantations of Taxus baccata, the generation of about 240 metric tons per year of biomass waste from the isolation of the baccatin derivative, and the 11 chemical transformations and seven isolations involved in the conversion to paclitaxel.

In the cell fermentation stage of the PCF process, calluses are propagated in a wholly aqueous medium in large fermenters under controlled conditions at ambient temperature and pressure. The feedstock for cell growth consists of renewable nutrients, sugars, amino acids, vitamins, and trace elements. This impressive example of the application of the principles of green chemistry to an industrial product was recognized by a 2004 Presidential Green Chemistry Challenge Award (C&EN, July 5, 2004, page 4).

Mike Williams
Kent, England