Taxol and Derivatives: A Biogenetic Hypothesis

Guéritte-Voegelein, Françoise; Guénard, Daniel; Potìer, Pierre

doi:10.1021/np50049a002

Cited by 103 publications

(51 citation statements)

References 26 publications

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“…Thus, acetylation of the C5α-hydroxyl, at some stage of the pathway, is considered a prelude to oxetane (D-ring) formation via the sequential conversion of the 5α-acetoxy-4(20)-ene functional grouping to the corresponding β-epoxide, with the last step most plausibly involving intramolecular migration of the 5α-acetoxy moiety in the process of oxirane ring expansion (Figure 4) (Guéritte-Voegelein et al, 1987;Floss and Mocek, 1995;Giner and Faraldos, 2003). The question therefore arises as to when the acetylation at C5α occurs on the pathway to Taxol (1) and its congeners.…”

Section: Discussionmentioning

confidence: 99%

Administering cultured Taxus cells with early precursors reveals bifurcations in the taxoid biosynthetic pathway

et al. 2007

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Feeding studies with Taxus suspension cells employing labeled 5α-hydroxytaxadiene and 5α,10β-dihydroxytaxadiene, and the corresponding 5α-acetate esters, demonstrated that acetylation at C5 of the monool precursor promotes the formation of 14β-hydroxy taxoids, such as taxuyunnanine C, at the expense of 13α-hydroxy taxoids, including Taxol and its congeners, but that the major bifurcation in taxoid biosynthesis, toward 13α-or 14β-hydroxy taxoids, occurs after 10β-hydroxylation of the taxane core.

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Section: Discussionmentioning

confidence: 99%

Administering cultured Taxus cells with early precursors reveals bifurcations in the taxoid biosynthetic pathway

et al. 2007

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“…Considering the age and isolation of the genus together with the extreme longevity of individual members (some yew trees live more than 3,000 years), it was believed that the Taxol metabolic pathway was unique to this genus. Members of the closely related genera Pseudotaxus and Austrotaxus do not synthesize Taxol, although simple taxanes lacking the oxetane or Dring structure have been isolated from Austrotaxus spicata, the only member of the genus Austrotaxus, which is regarded as a primitive ancestor of Taxus (Guéritte-Voegelein et al 1987). Pseudotaxus spp.…”

Section: Introductionmentioning

confidence: 99%

Getting to the bottom of Taxol biosynthesis by fungi

2013

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Taxol (paclitaxel) is a highly-oxygenated diterpenoid natural product first isolated from the pacific yew tree (Taxus brevifolia). It is one of the most widely used anticancer drugs. Soon after the discovery of its unique mode of action and the resulting high demand, an extensive search was initiated for alternative sources to replace the slow-growing and scarce pacific yew. Thus far, however, Taxol and related compounds have only been found in the genus Taxus, which comprises a small number of slow-growing plants with a broad but generally isolated geographical distribution. In 1993, Stierle and colleagues reported the independent biosynthesis of Taxol in an endophytic fungus isolated from Taxus brevifolia, which resulted in more than 160 subsequent publications and patents addressing the biosynthesis of Taxol and related taxanes by microorganisms. The literature on fungal taxane synthesis contains numerous inconsistencies, prompting us to thoroughly re-examine Taxol biosynthesis in endophytic fungi associated with Taxus spp. Using a combination of phytochemistry, molecular biology and genome sequencing, we were unable to find any evidence for independent taxane biosynthesis in any of the endophytes, including the isolate described in the original publication (Taxomyces andreanae) and several more recent isolates from Taxus trees. Our findings therefore resolve a long-standing mystery concerning the evolution of a complex terpenoid biosynthetic pathway in two distantly-related organisms.

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“…This latter process (Fig. 1 Inset) most plausibly (27) involves epoxidation of the C4-C20 double bond (likely mediated by cytochrome P450) and ring expansion with intramolecular migration of the C5␣-acetoxy group catalyzed by an isomerase (oxomutase) of unknown type. Oxetane formation likely precedes C9 oxidation and may precede the late pathway hydroxylation at C1 (17) such that the hypothetical intermediate of Fig.…”

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confidence: 99%

Random sequencing of an induced Taxus cell cDNA library for identification of clones involved in Taxol biosynthesis

Jennewein

Wildung

Chau

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

155

143

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Biosynthesis of the anticancer drug Taxol involves 19 enzymatic steps from the universal diterpenoid progenitor geranylgeranyl diphosphate derived by the plastidial methylerythritol phosphate pathway for isoprenoid precursor supply. To gain further insight about Taxol biosynthesis relevant to the improved production of this drug and to draw inferences about the organization, regulation, and origins of this complex natural product pathway, random sequencing of a cDNA library derived from Taxus cuspidata cells (induced for taxoid biosynthesis with methyl jasmonate) was undertaken. This effort revealed surprisingly high abundances for transcripts of several of the 12 defined genes of Taxol biosynthesis, yielded cDNAs encoding two previously uncharacterized cytochrome P450 taxoid hydroxylases, and provided candidate genes for all but one of the remaining seven steps of this extended sequence of reactions.paclitaxel ͉ Taxus cuspidata ͉ expressed sequence tags ͉ taxoid 10␤-hydroxylase

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Taxol and Derivatives: A Biogenetic Hypothesis

Abstract: Based on the structural differences of compounds isolated from various species of Taxus, this brief review suggests a biogenetic approach to taxol. This hypothesis could be of some help in the synthesis of this complex molecule exhibiting significant antitumor properties.

Cited by 103 publications

References 26 publications

Administering cultured Taxus cells with early precursors reveals bifurcations in the taxoid biosynthetic pathway

Administering cultured Taxus cells with early precursors reveals bifurcations in the taxoid biosynthetic pathway

Getting to the bottom of Taxol biosynthesis by fungi

Random sequencing of an induced Taxus cell cDNA library for identification of clones involved in Taxol biosynthesis

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