Biosynthesis of taxol

Eisenreich, W., Menhard, B., Hylands, P.J. et al. (1996) Studies on the biosynthesis of Taxol the taxane carbon skeleton is not of mevalonoid origin. Proceedings of the National Academy of Sciences of the United States of America, 93, 6431-6436. 

Huang, Q., Roessner, C.A., Croteau, R. and Scott, A.I. (2001) Engineering Escherichia coli for the synthesis of taxadiene, a key intermediate in the biosynthesis of Taxol. Bioorganic Medicinal Chemistry, 9, 2237-2242. 

Taxol is biosynthesized in 19 steps from GGPP that originates from precursors of the MEP pathway (Fig. 5). The biosynthesis of Taxol begins with the formation of the tricyclic diterpene skeleton of taxa-4(5),ll(12)-diene (17, 39). All genes for the enzymes in this early pathway have been identified in Taxus cuspidata and a taxa-4(5),ll(12)-diene synthase has been identified in several Taxus species. The mechanism of this di-TPS has been explored in detail (39). Taxa-4(5),ll(12)-diene is then hydroxylated by several cytochrome P450 taxoid oxygenases to yield a putative intermediate decorated with seven alcohol... 

The biosynthesis of taxol was not discussed in the body of this review, primarily because the subject had recently been reviewed. Some important new work has appeared during the past year, however, and so this area is briefly reviewed here. 

Floss HG, Mocek U (1995) Biosynthesis of Taxol. In Suffness M (ed) Taxol Science... 

Rohy J (1997) Biosynthesis of Taxol. Angew Chem Int Ed Engl 36 2190... 

Huang Q, Roessner CA, Croteau R, Scott AI (2001) Engineering Escherichia coli for the Synthesis of Taxadiene, a Key Intermediate in the Biosynthesis of Taxol. Bioorg Med Chem 9 2237... 

FIGURE 2.3 A simplified representation of the biosynthesis of Taxol . The first committed step is the cyclization of geranylgeranyl pyrophosphate to the taxane skeleton. A series of site- and enantio-selective hydroxylations then takes place, followed by further transformations. 

Paclitaxel, commonly known as Taxol (the registered trademark), is a powerful diterpenoid anticancer dmg with an annual market value of several billion dollars [15]. Taxol was first isolated and identified from the bark of Pacific yew, a slow-growing tree that is adapted to a forest shade environment in the Pacific Northwest of North America. Pathway of the biosynthesis of Taxol in Taxus has been primarily deciphered as in Fig. 88.6. 

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