The compound is then purified by one chromatographic step followed by crystallization. Compared to the semisynthesis method, PCF eliminates the need for many hazardous chemicals and saves a considerable amount of energy.In 1993, paclitaxel was discovered as a natural product in a newly described endophytic fungus living in the yew tree. It has since been reported in a number of other endophytic fungi, including Nodulisporium sylviforme, Alternaria taxi, Cladosporium cladosporioides MD2, Metarhizium anisopliae, Aspergillus candidus MD3, Mucor rouxianus, Chaetomella raphigera, Phyllosticta tabernaemontanae, Phomopsis, Pestalotiopsis pauciseta, Phyllosticta citricarpa, Podocarpus sp., Fusarium solani, Pestalotiopsis terminaliae, Pestalotiopsis breviseta, Botryodiplodia theobromae, Gliocladium sp., Alternaria alternata var. monosporus, Cladosporium cladosporioides, Nigrospora sp., Pestalotiopsis versicolor, and Taxomyces andreanae. However, there has been contradictory evidence for its production by endophytes, with other studies finding independent production is unlikely. Biosynthesis
Taxol is a tetracyclic diterpene, and the biosynthesis of diterpenes starts with a FPP molecule being elongated by the addition of an IPP molecule in order to form geranylgeranyl diphosphate (GGPP). The biosynthesis of Taxol contains nineteen steps. These 19 steps can be considered in several steps, with the first step being the formation of the taxane skeleton, which then undergoes a series of oxygenations. Following the oxygenations, two acetylations and a benzoylation occur on the intermediate. The oxygenation of the taxane core is believed to occur on C5 and C10, C2 and C9, C13 followed by C7, and a C1 hydroxylation later on in the pathway.
Society and culture
As of 2006, the cost to the NHS per patient in early breast cancer, assuming four cycles of treatment, was about £4,000 (approx. $6,000). Research
Caffeine has been speculated to inhibit paclitaxel-induced apoptosis in colorectal cancer cells.Aside from its direct clinical use, paclitaxel is used extensively in biological and biomedical research as a microtubule stabilizer. In general, in vitro assays involving microtubules, such as motility assays, rely on paclitaxel to maintain microtubule integrity in the absence of the various nucleating factors and other stabilizing elements found in the cell. For example, it is used for in vitro tests of drugs that aim to alter the behavior of microtubule motor proteins, or for studies of mutant motor proteins. Moreover, Paclitaxel has been used in vitro to inhibit insulin fibrillation; in a molar ratio of 10:1 (insulin:paclitaxel), it hindered insulin fibrillation near 70%. Iso-thermal titration calorimetry (ITC) findings indicated a spontaneous tendency of paclitaxel to interact with insulin through hydrogen bonds and van der Waals forces. Also, the inhibitory role of paclitaxel is attributed to its impact on the colloidal stability of protein solution, as it was observed that paclitaxel inhibited lysozyme fibrillation by inducing the formation of "off-pathway" oligomeric intermediates and increasing the colloidal stability subsequently. Paclitaxel is sometimes used for in vivo studies as well; it can be fed to test organisms, such as fruit flies, or injected into individual cells, to inhibit microtubule disassembly or to increase the number of microtubules in the cell.