Production of Taxol and its Analogues from Cell Cultures of Taxus wallichiana

Veeresham, Ciddi; Mamatha, R.; Babu, CH Prasad; Srisilam, Keshetty; Kokate, C. K.

doi:10.1076/phbi.41.6.426.17822

Cited by 19 publications

(10 citation statements)

References 12 publications

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“…Concentrations of Phe were selected according to preliminary studies as well as the available literature [4,22]. The cells were harvested on day 14.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Effect of phenylalanine on Taxol production and antioxidant activity of extracts of suspension-cultured hazel (Corylus avellana L.) cells

et al. 2012

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Taxol is produced by a few microorganisms and plants such as yew (Taxus sp.). Recent researches have shown that hazel (Corylus avellana L.) is also able to produce Taxol. In the present study, effects of different concentrations of phenylalanine (Phe) on the production of Taxol, antioxidant activity, and cytotoxic effects of extracts of suspension-cultured hazel cells were investigated. The cells were treated with different concentrations of Phe on day 7 of subculture and were harvested on day 14. The results showed that the amounts of Taxol and antioxidant activity were increased by increasing the phenylalanine supply. Interestingly, the cytotoxic effects of hazel cell extract were even stronger than that of pure Taxol (standard), suggesting hazel cell extract as a novel and suitable probe for treating human cancer. Application of phenylalanine to hazel cells exaggerates their effects.

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“…Concentrations of Phe were selected according to preliminary studies as well as the available literature [4,22]. The cells were harvested on day 14.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Effect of phenylalanine on Taxol production and antioxidant activity of extracts of suspension-cultured hazel (Corylus avellana L.) cells

et al. 2012

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“…The addition of phenylalanine, a precursor of the Taxol side-chain, increased Taxol production from plants (Veeresham et al, 2003) and fungi (Strobel et al, 1996a). Taxol production in P. microspora increased when phosphate was decreased and sodium benzoate was added (Li et al, 1998a).…”

Section: Introductionmentioning

confidence: 99%

Interactions between Co-Habitating fungi Elicit Synthesis of Taxol from an Endophytic Fungus in Host Taxus Plants

Soliman¹,

Raizada²

2013

Front. Microbio.

104

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Within a plant, there can exist an ecosystem of pathogens and endophytes, the latter described as bacterial and fungal inhabitants that thrive without causing disease to the host. Interactions between microbial inhabitants represent a novel area of study for natural products research. Here we analyzed the interactions between the fungal endophytes of Taxus (yew) trees. Fungal endophytes of Taxus have been proposed to produce the terpenoid secondary metabolite, Taxol, an anti-cancer drug. It is widely reported that plant extracts stimulate endophytic fungal Taxol production, but the underlying mechanism is not understood. Here, Taxus bark extracts stimulated fungal Taxol production 30-fold compared to a 10-fold induction with wood extracts. However, candidate plant-derived defense compounds (i.e., salicylic acid, benzoic acid) were found to act only as modest elicitors of fungal Taxol production from the endophytic fungus Paraconiothyrium SSM001, consistent with previous studies. We hypothesized the Taxus plant extracts may contain elicitors derived from other microbes inhabiting these tissues. We investigated the effects of co-culturing SSM001 with other fungi observed to inhabit Taxus bark, but not wood. Surprisingly, co-culture of SSM001 with a bark fungus (Alternaria) caused a ∼threefold increase in Taxol production. When SSM001 was pyramided with both the Alternaria endophyte along with another fungus (Phomopsis) observed to inhabit Taxus, there was an ∼eightfold increase in fungal Taxol production from SSM001. These results suggest that resident fungi within a host plant interact with one another to stimulate Taxol biosynthesis, either directly or through their metabolites. More generally, our results suggest that endophyte secondary metabolism should be studied in the context of its native ecosystem.

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“…These compounds not only perform critical functions in plant fitness (e.g., as plant growth regulators, defensive compounds, pollinator attractants) but also are extensively used as preservatives and flavor enhancers, analgesics, antiseptics, chemotherapeutics, and feed stocks for chemical syntheses (1)(2)(3)(4)(5). Despite its simple structure and widespread distribution, full understanding of the biochemical pathways leading to BA formation remains incomplete.…”

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confidence: 99%

Completion of the core β-oxidative pathway of benzoic acid biosynthesis in plants

Qualley¹,

Widhalm²,

Adebesin

et al. 2012

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

168

136

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Despite the importance of benzoic acid (BA) as a precursor for a wide array of primary and secondary metabolites, its biosynthesis in plants has not been fully elucidated. BA formation from phenylalanine requires shortening of the C 3 side chain by two carbon units, which can occur by a non–β-oxidative route and/or a β-oxidative pathway analogous to the catabolism of fatty acids. Enzymes responsible for the first and last reactions of the core BA β-oxidative pathway (cinnamic acid → cinnamoyl-CoA → 3-hydroxy-3-phenylpropanoyl-CoA → 3-oxo-3-phenylpropanoyl-CoA → BA-CoA) have previously been characterized in petunia, a plant with flowers rich in phenylpropanoid/benzenoid volatile compounds. Using a functional genomics approach, we have identified a petunia gene encoding cinnamoyl-CoA hydratase-dehydrogenase ( PhCHD ), a bifunctional peroxisomal enzyme responsible for two consecutively occurring unexplored intermediate steps in the core BA β-oxidative pathway. PhCHD spatially, developmentally, and temporally coexpresses with known genes in the BA β-oxidative pathway, and correlates with emission of benzenoid volatiles. Kinetic analysis of recombinant PhCHD revealed it most efficiently converts cinnamoyl-CoA to 3-oxo-3-phenylpropanoyl-CoA, thus forming the substrate for the final step in the pathway. Down-regulation of PhCHD expression in petunia flowers resulted in reduced CHD enzyme activity, as well as decreased formation of BA-CoA, BA and their derived volatiles. Moreover, transgenic lines accumulated the PhCHD substrate cinnamoyl-CoA and the upstream pathway intermediate cinnamic acid. Discovery of PhCHD completes the elucidation of the core BA β-oxidative route in plants, and together with the previously characterized CoA-ligase and thiolase enzymes, provides evidence that the whole pathway occurs in peroxisomes.

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Production of Taxol and its Analogues from Cell Cultures of Taxus wallichiana

Cited by 19 publications

References 12 publications

Effect of phenylalanine on Taxol production and antioxidant activity of extracts of suspension-cultured hazel (Corylus avellana L.) cells

Effect of phenylalanine on Taxol production and antioxidant activity of extracts of suspension-cultured hazel (Corylus avellana L.) cells

Interactions between Co-Habitating fungi Elicit Synthesis of Taxol from an Endophytic Fungus in Host Taxus Plants

Completion of the core β-oxidative pathway of benzoic acid biosynthesis in plants

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