ABSTRACT
More than almost any other commercially useful plant secondary metabolite, Taxol has presented a formidable challenge to the efforts to devise an economically viable and sustainable process for its commercial production. The complexity of its structure does not bode well for success of the extensive efforts to develop a commercially feasible chemical total synthesis. Thus, at least for some time to come, the industrial production of Taxol will have to rely on biosynthesis of at least the complex diterpene moiety. As detailed in chapter 5 of this text, a medium-range solution of the problem of production of Taxol and analogues has been developed based on semisynthesis from 10-deacetylbaccatin-in which can be extracted from a renewable resource, the needles of European and Himalayan yew. However, in the long run it would be highly desirable to be able to produce Taxol and analogues thereof by a process which does not have to rely on the extraction of plant material but can rather be carried out under entirely controllable conditions. Such a biotechnological process may be based on a plant cell culture fermentation, a microbial fermentation with a genetically engineered organism, or it may be a hybrid process combining either of these two approaches with chemical steps and/or the use of isolated enzymes. The development of such a process would be based on, or would at least greatly benefit from, detailed knowledge of the biosynthetic pathway by which the plant assembles Taxol and by characterization of the enzymes catalyzing the various reactions involved and of the genes coding for them. Although the few biotechnological processes for the commercial production of plant secondary metabolites currently available were all developed empirically, it seems likely that in the future genetic engineering of metabolic pathways based on an understanding of the biosynthesis will play an increasingly prominent role. It is in this context that the biosynthesis of Taxol is of interest as a starting point for the future development of alternative biotechnological production processes for Taxol and the next generations of Taxol analogues.
