Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards Taxol (Paclitaxel) production

Engels, Benedikt; Dahm, Pia; Jennewein, Stefan

doi:10.1016/j.ymben.2008.03.001

Cited by 333 publications

(215 citation statements)

References 30 publications

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“…Chemical synthesis of taxol has been difficult because of its complex chemical structure [102] while its microbial production was also difficult for its unusually long biosynthetic pathway. [103] Therefore, the intermediates of taxol such as taxadiene and oxygenated taxanes were biosynthesized by metabolically engineered E. coli [104] or yeast, [105] which then went through chemical processes for the final product synthesis.…”

Section: Semi-synthesis Processmentioning

confidence: 99%

Metabolic Engineering of Microorganisms for the Production of Natural Compounds

Park

Yang

et al. 2017

Adv. Biosys.

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Natural products have been attracting much interest around the world for their diverse applications, especially in drug and food industries. Plants have been a major source of many different natural products. However, plants are affected by weather and environmental conditions and their successful extraction is rather limited. Chemical synthesis is inefficient due to the complexity of their chemical structures involving enantioselectivity and regioselectivity. For these reasons, an alternative means of overproducing valuable natural products using microorganisms has emerged. In recent years, various metabolic engineering strategies have been developed for the production of natural products by microorganisms. Here, the strategies taken to produce natural products are reviewed. For convenience, natural products are classified into four main categories: terpenoids, phenylpropanoids, polyketides, and alkaloids. For each product category, the strategies for establishing and rewiring the metabolic network for heterologous natural product biosynthesis, systems approaches undertaken to optimize production hosts, and the strategies for fermentation optimization are reviewed. Taken together, metabolic engineering has enabled microorganisms to serve as a prominent platform for natural compounds production. This article examines both the conventional and novel strategies of metabolic engineering, providing general strategies for complex natural compound production through the development of robust microbial‐cell factories.

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Section: Semi-synthesis Processmentioning

confidence: 99%

Metabolic Engineering of Microorganisms for the Production of Natural Compounds

Park

Yang

et al. 2017

Adv. Biosys.

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“…Heterologous gene expression successfully occurred in Saccharomyces cerevisiae by insertion of Taxol ® producing plant host (Taxus chinensis) gene taxadiene synthase. This breakthrough research led to high-level expression of the taxadiene synthase gene resulting in a 40-fold increase in taxadiene upto 8.7 mg/L alongwith considerable increase in geranylgeraniol (Engels et al, 2008). In a recent study from India authors demonstrated that fungal taxol isolated from Cladosporium oxysporum could inhibit breast cancer cell line by regulating multiple apoptotic signalling pathways (Raj et al, 2015).…”

Section: Chemistry and Mode Of Action:-mentioning

confidence: 99%

Endosymbionts: A Continuing Source of Cytotoxic Metabolite Taxol.

Chowdhary¹,

Jangir²,

Sharma³

2017

IJAR

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“…With regards to Taxol, both S. cerevisiae and E. coli have been used to generate early stage intermediates in the downstream pathway (Ajikumar et al 2010;Dejong et al 2006;Engels et al 2008;Huang et al 2001). Both hosts are strong candidates for heterologous biosynthesis as a function of their rapid growth rates (compared to plant cells) and range of molecular biology tools to facilitate and optimize metabolic engineering efforts.…”

Section: Heterologous Biosynthetic Logic: Upstream and Downstream Commentioning

confidence: 99%

“…2). A later effort by Stefan Jennewein's group to optimize the heterologous production of taxadiene from S. cerevisiae was notable for the application of metabolic engineering to improve biosynthetic substrate availability, the use of a codon-optimized taxadiene synthase gene, and final taxadiene levels of 8.7 mg/L (Engels et al 2008).…”

Section: Challenges and Options Associated With The Heterologous Implmentioning

confidence: 99%