CYCLIZATION OF GERANYLGERANYL DIPHOSPHATE TO TAXA-4(5),11(12)-DIENE IS THE COMMITTED STEP OF TAXOL BIOSYNTHESIS IN PACIFIC YEW
CYCLIZATION OF GERANYLGERANYL DIPHOSPHATE TO TAXA-4(5),11(12)-DIENE IS THE COMMITTED STEP OF TAXOL BIOSYNTHESIS IN PACIFIC YEW
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DOI：
10.1074/jbc.270.15.8686
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发表时间：
1995-04-14
影响因子：
4.8
通讯作者：
CROTEAU, R
中科院分区：
文献类型：
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作者：
KOEPP, AE;HEZARI, M;CROTEAU, R
紫杉醇的生物合成紫杉醇（paclitaxel）及相关税收援助短叶红豆杉（Taxus brevifolia）被认为涉及香叶基香叶基二磷酸环化为紫杉二烯，随后是该二萜烯烃中间体的广泛氧化。来自紫杉幼苗茎的无细胞制剂催化[1-H-3]香叶基香叶基二磷酸转化为环状二萜烯烃，当与茎段一起孵育时，以良好的放射化学产率转化为几种高度官能化的紫杉烷，包括10-脱乙酰基浆果赤霉素III和紫杉醇本身。将标记的烯烃添加到紫杉树皮提取物中，然后进行放射化学引导的分级分离，提供了足够的产物以通过二维NMR光谱方法建立紫杉-4（5），11（12）-二烯的结构。因此，紫杉醇生物合成中的第一个专用步骤是将通用的二萜类前体香叶基香叶基二磷酸转化为紫杉-4（5），11（12）-二烯，而不是先前提出的4（20），11（12）-二烯异构体，这是在这些位置具有双键的紫杉烷丰度的基础。带有4（20）-烯-5-氧基官能团的紫杉烷衍生物的非常常见的出现，以及带有4（5）-双键的含氧衍生物的缺乏，表明紫杉二烯的C-5羟基化和双键的烯丙基重排是这种烯烃中间体转化为紫杉醇的早期步骤。
The biosynthesis of taxol (paclitaxel) and related tax aids in Pacific yew (Taxus brevifolia) is thought to involve the cyclization of geranylgeranyl diphosphate to a taxadiene followed by extensive oxygenation of this diterpene olefin intermediate, A cell-free preparation from sapling yew stems catalyzed the conversion of [1-H-3]geranylgeranyl diphosphate to a cyclic diterpene oIefin that, when incubated with stem sections, was converted in good radiochemical yield to several highly functionalized taxanes, including 10-deacetyl baccatin III and taxol itself. Addition of the labeled olefin to a yew bark extract, followed by radiochemically guided fractionation, provided sufficient product to establish the structure as taxa-4(5),11(12)-diene by two-dimensional NMR spectroscopic methods, Therefore, the first dedicated step in taxol biosynthesis is the conversion of the universal diterpenoid precursor geranylgeranyl diphosphate to taxa-4(5),11(12)-diene, rather than to the 4(20),11(12)-diene isomer previously suggested an the basis of the abundance of taxoids with double bonds in these positions. The very common occurrence of taxane derivatives bearing the 4(20)-ene-5-oxy functional grouping, and the lack of oxygenated derivatives bearing a 4(5)-double bond, suggest that hydroxylation at C-5 of taxadiene with allylic rearrangement of the double bond is an early step in the conversion of this olefin intermediate to taxol.