Taxol Biosynthesis: An Update

Hezari, Mehri; Croteau, Rodney

doi:10.1055/s-2006-957684

Cited by 94 publications

(60 citation statements)

References 15 publications

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“…[49][50][51] The first committed step comprises the cyclization of GGPP to taxa-4(5), 11(12)-diene by TS. 52 Taxadiene is transformed by eight cytochrome P450-mediated oxygenations and two CoA-dependent acylations, the oxetane ring formation and oxidation at C9 to yield 10-deacetyl baccatin III.…”

Section: Genes Of the Paclitaxel Biosynthetic Pathwaymentioning

confidence: 99%

“…The genes encoding enzymes involved in several steps of the paclitaxel biosynthetic pathway have been isolated and functionally expressed in Escherichia coli and Saccharomyces cerevisiae. 49,51,[61][62][63][64][65][66][67][68] The enzymes included taxane 2a-O-benzoyltransferase, taxa-4(5),11(12)-diene synthase responsible for cyclization of the universal diterpenoid precursor GGPP to taxa-4(5), 11(12)-diene, the cytochrome P450 taxoid 2a-, 5a-, 7b-, 10b-and 13a-hydroxylases responsible for regiospecific oxygenation on the taxadiene core, the acyl/aroyl CoAdependent transferases responsible for esterification at the C2-O, C5-O and C10-O positions, and several steps of C13-side-chain assembly. In addition, the biosynthesis of taxadiene has been achieved in cell-free extracts of E. coli overexpressing the genes encoding for isopentenyl diphosphate isomerase, GGPP synthase and TS.…”

Section: Heterologous Expression In Bacteria and Yeastsmentioning

confidence: 99%

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Microbial paclitaxel: advances and perspectives

et al. 2010

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Paclitaxel is a potent and widely used antitumor agent. Considerable worldwide research efforts have been carried out on different production alternatives. Since the description of the first paclitaxel-producing fungi, more than 15 years ago, microorganisms have been investigated as potential alternatives for an environmentally acceptable, relatively simple and inexpensive method to produce paclitaxel. However, in spite of significant research on paclitaxel-producing microorganisms, no commercial fermentation process has been implemented up to now. The aim of this study is to review the present status of research on paclitaxel-producing microorganisms and the ongoing efforts to develop heterologous paclitaxel biosynthesis, and analyze the perspectives of microbial fermentation for paclitaxel production.

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Section: Genes Of the Paclitaxel Biosynthetic Pathwaymentioning

confidence: 99%

Section: Heterologous Expression In Bacteria and Yeastsmentioning

confidence: 99%

Microbial paclitaxel: advances and perspectives

et al. 2010

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“…Recently, taxol has been reported to be useful in treating neurodegenerative diseases such as Alzheimer's disease. The main shortcoming of taxol seems to be its mass production, which can be resolved by exploring microbial synthesis of paclitaxel since total chemical synthesis proves problematic due to its complex structure [25][26][27]. to trigger the ionization of the diphosphate group of their substrate, which initiate catalysis by producing a carbocation.…”

Section: Taxolmentioning

confidence: 99%

A Glimpse into the Biosynthesis of Terpenoids

Abdallah¹,

Quax

2017

KLS

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Terpenoids represent the largest class of natural products with a diverse array of structures and functions. Many terpenoids have reported therapeutic properties such as antimicrobial, anti-inflammatory, immunomodulatory and chemotherapeutic properties making them of great interest in the medical field. Also, they are widely used in the flavors and fragrances industries, in addition to being a source of biofuels. Terpenoids suffer from low natural yields and complicated chemical synthesis, hence the need for a more sustainable production method. Metabolic engineering provide an excellent opportunity to construct microbial cell factories producing the desired terpenoids. The biosynthetic mevalonate and non-mevalonate pathways involved in the production of terpenoid precursors are fully characterized so exploring methods to improve their flux would be the first step in creating a successful cell factory. The complexity and diversity of terpenoid structures depends mainly on the action of the terpene synthases responsible for their synthesis. These enzymes are classified into different classes and gaining insight into their catalytic mechanism will be useful in designing approaches to improve terpenoid production. This review focuses on the biosynthesis and biodiversity of terpenoids, understanding the terpene synthase enzyme family involved in their synthesis and the engineering efforts to create microbial cell factories for terpenoid production.

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“…It is required 19 steps from the universal diterpenoid geranylgeranyl diphosphate (GGPP). Hence it is not involved in the commercial production [24,25]. A new method for the semisynthesis of Taxol from baccatin III has been attained via a dioxo-oxathiazolidine intermediate [26].…”

Section: Chemical Synthesismentioning

confidence: 99%

New Approach To Improve Taxol Biosynthetic

Badi¹,

Abdoosi²,

Farzin³

2015

TJS

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Taxol (Generic name for paclitaxel) is a complicated diterpene compound that is initially isolated from yew plants. Taxol is one of the most exciting natural ingredients to treat various cancers, including breast cancer, ovarian carcinoma, melanoma, and lung cancer. Limited number of yew trees, low content of taxol in plant tissue, slow growing and killing the tree to bark harvesting are significant restrictions that have led to the supply and availability of this important substance faced with challenges. Many attempts to complete synthesis, semi-synthesis, finding new source e.g alternative spices, other plant, microorganisms and establishment of the cell suspension cultures have been carried out. Cell culture is an appropriate strategy for stable production by using a small part of the plant as explants. Elicitors such as methyl jasmonate family compounds are powerfull stimulator for production of taxol. Methyl jasmonate increases the amount of taxol by enhancing the expression levels of taxol biosynthesis enzymes such as Geranyl-geranyl pyrophosphate synthase (GGPPs) and taxadienesynthesis (TDS). New approach including genetic and metabolic engineering can be led to increasing the taxol production by the over-expression of genes controlling limiting steps or by suppressing the undesired taxanes by employing antisense technology. The yew-coding genes associated with the production of taxol have been cloned. However, genetic manipulation strategies are not yet complete. This paper reviews the various ways to improve Taxol production.

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Taxol Biosynthesis: An Update

Cited by 94 publications

References 15 publications

Microbial paclitaxel: advances and perspectives

Microbial paclitaxel: advances and perspectives

A Glimpse into the Biosynthesis of Terpenoids

New Approach To Improve Taxol Biosynthetic

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