Plant cell fermentation

The above definition of classical biotechnological processes can easily be adapted to the concept of molecular farming. With plant cell fermentation the analogy is ob-... 

A brilliant example for the industrial-scale application of plant cell fermentation is the new process for the production of the anticancer drug paclitaxel developed by Bristol-Myers Squibb (see Figure 15.1). It starts with clusters of paclitaxel producing cells from the needles of the Chinese yew, T. chinensis, and was introduced in 2002. The API is isolated from the fermentation broth and is purified by chromatography and crystallization. The new process substitutes the previously used semisynthetic route. It started with lO-deacetylbaccatin(III), a compound that contains most of the structural complexity of paclitaxel and can be extracted from leaves and twigs of the European yew, T. baccata. The chemical process to convert 10-deacetylbaccatin(III) to paclitaxel is complex. It includes 11 synthetic steps and has a modest yield. 

Figure 15.1 Plant cell fermentation process for paclitaxel. Source Bristol-Myers Squibb.

The Taxol Story-Development of a Green Synthesis via Plant Cell Fermentation ... 

Figure 7.7 Plant cell fermentation and extraction process.

Ritter, S.K. (2004) Chem. Eng. News, 82 (27), 4. Also Development of Green Synthesis for Taxol Manufacture via Plant Cell Fermentation and Extraction submitted for 2004 EPA Greener Synthetic Chemistry award, http //www. epa.gov/greenchemistry/pubs/pgcc/ winners/gspa04.html (accessed May 2009). 

Mountford, P.G. (2006) Development of a Green Synthesis for Taxol Manufac-mre via Plant Cell Fermentation and Extraction. Hosted by Colegio de Quimicos de Puerto Rico, Weshn RioMar, PR, Aug. 15-18. 

Constabel, F., "Principles Underlying the Use of Plant Cell Fermentation for Secondary Metabolite Production," Biochem. Cell. Biol. 66 (1988) 658-664. 

FIGURE 5.3 One of the most potent chemotherapeutic agents used in cancer, Taxol is semisynthesized from 10-DAB. 10-DAB is isolated from the needles of the English yew or is produced by a plant cell fermentation process. 

Since the 1990s, paclitaxel has also been produced by plant cell fermentation. 

Plants have also provided a key source of potential cancer treatments. A well-known example is paclitaxel (Taxol ), isolated from the bark of the Pacific yew tree, which has become a blockbuster drug and analogues have also been approved for use that demonstrate improved efficacy (Fig. 1.4) [6]. Taxol also provides an excellent example to illustrate the challenges that remain in total synthesis. Numerous examples of the total synthesis of Taxol have been reported [7-13]. However, the overall yield and the number of steps required means it is not economically viable to synthesise the quantities required for its medicinal application. It is therefore obtained industrially via a semi-synthetic route starting from 10-deacetylbaccatin HI, a biosynthetic precursor, which can be isolated, in much larger quantities than Taxol itself, from the leaves of a different species of yew tree. More recently however, a plant cell fermentation approach has been developed for the industrial production of Taxol. 

Bristol-Myers Squibb Company sold 1.6 bilhon worth taxol in 2000. Phyton, Inc. in Ithaca, New York, is developing a technology to produce taxol by plant cell fermentation and is now collaborating with Bristol-Myers Squibb. 

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