Editing Paclitaxel (section)

===Biosynthesis===
[[File:Biosynthesis of Taxol.png|thumb|class=skin-invert-image|Biosynthesis of Taxol]]
Taxol is a tetracyclic [[diterpene]], and the biosynthesis of diterpenes starts with an FPP molecule being elongated by the addition of an IPP molecule in order to form geranylgeranyl diphosphate ([[GGPP]]).<ref name=":2">{{cite book| vauthors = Dewick PM |title=Medicinal Natural Products|date=6 February 2009|publisher=John Wiley & Sons, Ltd|isbn=978-0-470-74276-1|location=Chichester, UK |language=en |doi=10.1002/9780470742761 }}</ref> The biosynthesis of Taxol contains nineteen steps.<ref>{{cite journal | vauthors = Howat S, Park B, Oh IS, Jin YW, Lee EK, Loake GJ | title = Paclitaxel: biosynthesis, production and future prospects | journal = New Biotechnology | volume = 31 | issue = 3 | pages = 242–245 | date = May 2014 | pmid = 24614567 | doi = 10.1016/j.nbt.2014.02.010 }}</ref> 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. Later in the pathway, an oxidation at C9 forms a ketone functional group and an oxetane, forming the intermediate baccatin III. The final steps of the pathway include the formation of a C13-side chain which is attached to baccatin III.<ref>{{cite journal | vauthors = Croteau R, Ketchum RE, Long RM, Kaspera R, Wildung MR | title = Taxol biosynthesis and molecular genetics | journal = Phytochemistry Reviews | volume = 5 | issue = 1 | pages = 75–97 | date = February 2006 | pmid = 20622989 | pmc = 2901146 | doi = 10.1007/s11101-005-3748-2 | bibcode = 2006PChRv...5...75C }}</ref> The biosynthesis of Taxol is illustrated in more detail in the figure, with steps 1-7 all occurring in the enzyme [[taxadiene synthase]] (TS on the figure). Taxol's biosynthesis begins with E,E,E-GGPP losing pyrophosphate via an [[SN1]] mechanism (step 1 in the figure). The double-bond attacks the cation via electrophilic addition, yielding a tertiary cation and creating the first ring closure (step 2). Another electrophilic attack occurs, further cyclizing the structure by creating the first 6-membered ring and creating another tertiary cation (step 3). An intramolecular proton transfer occurs, attacking the verticillyl cation (step 4) and creating a double bond, yielding a tertiary cation. An electrophilic cyclization occurs in step 5, and an intramolecular proton transfer attacks the taxenyl cation (step 6). This forms the fused ring structure intermediate known as taxadiene. Taxadiene then undergoes a series of 10 oxidations via [[NADPH]], forming the intermediate taxadiene-5α-acetoxy-10β-ol (multiple steps later in the figure). A series of hydroxylations and esterficiations occur, forming the intermediate 10-deacetyl-baccatin III, which undergoes a further series of esterifications and a side-chain hydroxylation.<ref name=":2" /> This finally yields the product taxol.