Biosynthetic building blocks of taxanes

Zamir, Lolita O.; Nedea, Maria Elena; Garneau, François-Xavier

doi:10.1016/s0040-4039(00)79141-6

Cited by 56 publications

(21 citation statements)

References 8 publications

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“…The papers of Lansing et al (1991) and Zamir et al (1992) were the first that described feeding experiments with labelled mevalonate, obtaining high rates of radioactively labelled paclitaxel. Their findings opened up the possibility of enhancing taxoid accumulation through precursors feeding that resulted in more efficient enzymatic processes.…”

Section: Sugar Feeding Strategymentioning

confidence: 99%

In vitro culture of Taxus sp.: strategies to increase cell growth and taxoid production

Sabater-Jara

Tudela²,

López-Pérez³

2010

Phytochem Rev

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Interest in Taxus species has increased since paclitaxel, an anticancer drug, was isolated from the bark of Taxus brevifolia (Pacific yew) in the 1960's. Great effort has been carried out to establish an efficient callus cultures of Taxus species. Culture media must be optimized for each Taxus species, and in general, there is no one method that guarantees success for Taxus cultures. The source of explant, culture medium composition and the growth regulators used appear to affect callus initiation and maintenance. Research effort has focused on obtaining a cell culture that exhibits good growth and a high rate of taxoid accumulation. In this sense, many strategies have been employed to stimulate taxoid production without affecting cell growth. In an attempt to scale-up cell culture, problems such us shear stress, oxygen supply and gas composition have been studied. A more detailed knowledge of the pathway and the fluxes of intermediates towards taxane accumulation will be key factors to obtain cell lines with increased taxane accumulation through metabolic engineering.

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Section: Sugar Feeding Strategymentioning

confidence: 99%

In vitro culture of Taxus sp.: strategies to increase cell growth and taxoid production

Sabater-Jara

Tudela²,

López-Pérez³

2010

Phytochem Rev

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“…Zamir et al (1992) showed that the incubation of ground needles of T. canadensis with (3RS) (5RS) (5-3H) mevaionate resulted in the incorporation of radioactivity into paclitaxel. In addition, a terpene cyclase has been isolated and purified from the bark tissue of T. brevifolia which converts geranylgeranyl pyrophosphate into 4(5) 11 (12)-taxadiene.…”

Section: Cell Growth and Taxoid Productionmentioning

confidence: 99%

Taxus sp. cell, tissue and organ cultures as alternative sources for taxoids production: a literature survey

Jaziri

Zhiri

Guo

et al. 1996

Plant Cell Tiss Organ Cult

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The literature concerning the tissue culture of Taxus sp. as an alternative source for taxoid production is reviewed.The aim of this review is to summarize and discuss the progress achieved with the approaches and methods used for the establishment of various Taxus culture systems, the methods used for the evaluation of taxoid production, the multiple factors which control taxoid production and the feasibility of the in vitro production of taxoids on a commercial scale.

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“…Although it has been studied for more than 10 years, the biosynthetic origin of taxol has still not been totally elucidated. Previous work carried out by Lansing et al (1991) and Zamir et al (1992) showed that when supplied with labeled mevalonate, Taxus plants could produce high rates of radioactively labeled taxol, indicating that taxol originated from the mevalonate pathway. Subsequent studies of taxol biosynthesis have showed conclusively that the taxane ring system is synthesized via the plastidial 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway (Eisenreich et al 1996).…”

mentioning

confidence: 97%

A New Farnesyl Diphosphate Synthase Gene fromTaxus mediaRehder: Cloning, Characterization and Functional Complementation

Liao

Chen

Gong

et al. 2006

JIPB

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Farnesyl diphosphate synthase (FPS; EC 2.5.1.10) catalyzes the production of 15-carbon farnesyl diphosphate which is a branch-point intermediate for many terpenoids. This reaction is considered to be a ratelimiting step in terpenoid biosynthesis. Here we report for the first time the cloning of a new full-length cDNA encoding farnesyl diphosphate synthase from a gymnosperm plant species, Taxus media Rehder, designated as TmFPS1. The full-length cDNA of TmFPS1 (GenBank accession number: AY461811) was 1 464 bp with a 1 056-bp open reading frame encoding a 351-amino acid polypeptide with a calculated molecular weight of 40.3 kDa and a theoretical pI of 5.07. Bioinformatic analysis revealed that TmFPS1 contained all five conserved domains of prenyltransferases, and showed homology to other FPSs of plant origin. Phylogenetic analysis showed that farnesyl diphosphate synthases can be divided into two groups: one of prokaryotic origin and the other of eukaryotic origin. TmFPS1 was grouped with FPSs of plant origin. Homologybased structural modeling showed that TmFPS1 had the typical spatial structure of FPS, whose most prominent structural feature is the arrangement of 13 core helices around a large central cavity in which the catalytic reaction takes place. Our bioinformatic analysis strongly suggests that TmFPS1 is a functional gene. Southern blot analysis revealed that TmFPS1 belongs to a small FPS gene family in T. media. Northern blot analysis indicated that TmFPS1 is expressed in all tested tissues, including the needles, stems and roots of T. media. Subsequently, functional complementation with TmFPS1 in a FPS-deficient mutant yeast demonstrated that TmFPS1 did encode farnesyl diphosphate synthase, which rescued the yeast mutant. This study will be helpful in future investigations aiming at understanding the detailed role of FPS in terpenoid biosynthesis flux control at the molecular genetic level.

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Biosynthetic building blocks of taxanes

Cited by 56 publications

References 8 publications

In vitro culture of Taxus sp.: strategies to increase cell growth and taxoid production

In vitro culture of Taxus sp.: strategies to increase cell growth and taxoid production

Taxus sp. cell, tissue and organ cultures as alternative sources for taxoids production: a literature survey

A New Farnesyl Diphosphate Synthase Gene fromTaxus mediaRehder: Cloning, Characterization and Functional Complementation

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