Taxanes with C-5-amino-side chains from the needles of Taxus canadensis

Shi, Qing; Ji, Xiuhong; Lesimple, Alain; Sauriol, Françoise; Zamir, Lolita O.

doi:10.1016/j.phytochem.2004.08.042

Cited by 11 publications

(4 citation statements)

References 24 publications

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“…None of these 3(11)-cyclotaxanes has a 5(12) cyclic ether. However, another cyclotaxane with a 4(13) cyclic ether bond was recently identified from Taxus canadensis needles (41). These observations tend to confirm that the cyclase activity of CYP725A4 or closely related enzymes is biologically relevant in the biosynthesis of cyclotaxane derivatives in yew trees.…”

Section: Discussionmentioning

confidence: 68%

CYP725A4 from Yew Catalyzes Complex Structural Rearrangement of Taxa-4(5),11(12)-diene into the Cyclic Ether 5(12)-Oxa-3(11)-cyclotaxane

Rontein

Onillon

Herbette

et al. 2008

Journal of Biological Chemistry

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Taxa-4(5),11(12)-diene is the first committed precursor of functionalized taxanes such as paclitaxel, a successful anticancer drug. Biosynthesis of taxanes in yew involves several oxidations, a number of which have been shown to be catalyzed by cytochrome P-450 oxygenases. Hydroxylation of the C-5␣ of taxa-4(5),11(12)-diene is believed to be the first of these oxidations, and a gene encoding a taxa-4(5),11(12)-diene 5␣-hydroxylase (CYP725A4) was recently described (Jennewein, S., Long, R. M., Williams, R. M., and Croteau, R. (2004) Chem. Biol. 11, 379 -387). In an attempt to produce the early components of the paclitaxel pathway by a metabolic engineering approach, cDNAs encoding taxa-4(5),11(12)-diene synthase and CYP725A4 were introduced in Nicotiana sylvestris for specific expression in trichome cells. Their co-expression did not lead to the production of the expected 5␣-hydroxytaxa-4(20),11(12)-diene. Instead, taxa-4(5),11(12)-diene was quantitatively converted to a novel taxane that was purified and characterized. Its structure was determined by NMR analysis and found to be that of 5(12)-oxa-3(11)-cyclotaxane (OCT) in which the eight-carbon B-ring from taxa-4(5),11(12)-diene is divided into two fused five-carbon rings. In addition, OCT contains an ether bridge linking C-5 and C-12 from opposite sides of the molecule. OCT was also the sole major product obtained after incubation of taxa-4(5),11(12)-diene with NADPH and microsomes prepared from recombinant yeast expressing CYP725A4. The rearrangement of the taxa-4(5),11(12)-diene ring system is thus mediated by CYP725A4 only and does not rely on additional enzymes or factors present in the plant. The complex structure of OCT led us to propose a reaction mechanism involving a sequence of events so far unknown in P-450 catalysis.

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Section: Discussionmentioning

confidence: 68%

CYP725A4 from Yew Catalyzes Complex Structural Rearrangement of Taxa-4(5),11(12)-diene into the Cyclic Ether 5(12)-Oxa-3(11)-cyclotaxane

Rontein

Onillon

Herbette

et al. 2008

Journal of Biological Chemistry

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“…Taxanes with different C-5-amino-side chains produce different fragment ions (Scheme ) . The relative abundance of the molecular ion is high and sometimes displayed as the base peak.…”

Section: Ms Features Of Taxanesmentioning

confidence: 99%

“…222,225,227,231 233 Taxanes with different C-5-amino-side chains produce different fragment ions (Scheme 17). 234 The relative abundance of the molecular ion is high and sometimes displayed as the base peak. An ion peak at m/z 120 suggests that there is only one methyl group attached to the nitrogen of side chain, whereas m/z 134 suggests there are two methyl groups.…”

Section: Ms Features Of Taxanesmentioning

confidence: 99%

Natural Taxanes: Developments Since 1828

et al. 2011

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“…132 Taxanes with amino acid side chains at C-5 have been obtained from T. canadensis. 133 Some further taxanes containing an oxetane ring have been isolated 134 from T. chinensis, whilst the rearrangement product 83 was obtained 135 from needles of T. cuspidata.…”

Section: Taxanesmentioning

confidence: 99%