Engineering Isoprenoid Biosynthesis in Artemisia annua L. for the Production of Taxadiene: A Key Intermediate of Taxol

Taxadiene is the first committed precursor to paclitaxel, marketed as Taxol, arguably the most important anticancer agent against ovarian and breast cancer. In Taxus, taxadiene is directly synthesized from geranylgeranyl diphosphate (GGPP) that is the common precursor for diterpenoids and is found i...

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Main Authors: Meiya Li, Fusheng Jiang, Xiangli Yu, Zhiqi Miao
Format: Article
Language:English
Published: Hindawi Limited 2015-01-01
Series:BioMed Research International
Online Access:http://dx.doi.org/10.1155/2015/504932
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spelling doaj-4ee1533406494fd48ce31ac13b79f9b62020-11-25T00:34:32ZengHindawi LimitedBioMed Research International2314-61332314-61412015-01-01201510.1155/2015/504932504932Engineering Isoprenoid Biosynthesis in Artemisia annua L. for the Production of Taxadiene: A Key Intermediate of TaxolMeiya Li0Fusheng Jiang1Xiangli Yu2Zhiqi Miao3Fudan-SJTU-Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaInstitute of Biotechnology, College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaFudan-SJTU-Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaFudan-SJTU-Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, ChinaTaxadiene is the first committed precursor to paclitaxel, marketed as Taxol, arguably the most important anticancer agent against ovarian and breast cancer. In Taxus, taxadiene is directly synthesized from geranylgeranyl diphosphate (GGPP) that is the common precursor for diterpenoids and is found in most plants and microbes. In this study, Artemisia annua L., a Chinese medicinal herb that grows fast and is rich in terpenoids, was used as a genetic engineering host to produce taxadiene. The TXS (taxadiene synthase) gene, cloned from Taxus and inserted into pCAMBIA1304, was transformed into Artemisia annua L. using the Agrobacterium tumefaciens-mediated method. Thirty independent transgenic plants were obtained, and GC-MS analysis was used to confirm that taxadiene was produced and accumulated up to 129.7 μg/g dry mass. However, the high expression of TXS did not affect plant growth or photosynthesis in transgenic Artemisia annua L. It is notable that artemisinin is produced and stored in leaves and most taxadiene accumulated in the stem of transgenic Artemisia annua L., suggesting a new way to produce two important compounds in one transgenic plant: leaves for artemisinin and stem for taxadiene. Overall, this study demonstrates that genetic engineering of the taxane biosynthetic pathway in Artemisia annua L. for the production of taxadiene is feasible.http://dx.doi.org/10.1155/2015/504932
collection DOAJ
language English
format Article
sources DOAJ
author Meiya Li
Fusheng Jiang
Xiangli Yu
Zhiqi Miao
spellingShingle Meiya Li
Fusheng Jiang
Xiangli Yu
Zhiqi Miao
Engineering Isoprenoid Biosynthesis in Artemisia annua L. for the Production of Taxadiene: A Key Intermediate of Taxol
BioMed Research International
author_facet Meiya Li
Fusheng Jiang
Xiangli Yu
Zhiqi Miao
author_sort Meiya Li
title Engineering Isoprenoid Biosynthesis in Artemisia annua L. for the Production of Taxadiene: A Key Intermediate of Taxol
title_short Engineering Isoprenoid Biosynthesis in Artemisia annua L. for the Production of Taxadiene: A Key Intermediate of Taxol
title_full Engineering Isoprenoid Biosynthesis in Artemisia annua L. for the Production of Taxadiene: A Key Intermediate of Taxol
title_fullStr Engineering Isoprenoid Biosynthesis in Artemisia annua L. for the Production of Taxadiene: A Key Intermediate of Taxol
title_full_unstemmed Engineering Isoprenoid Biosynthesis in Artemisia annua L. for the Production of Taxadiene: A Key Intermediate of Taxol
title_sort engineering isoprenoid biosynthesis in artemisia annua l. for the production of taxadiene: a key intermediate of taxol
publisher Hindawi Limited
series BioMed Research International
issn 2314-6133
2314-6141
publishDate 2015-01-01
description Taxadiene is the first committed precursor to paclitaxel, marketed as Taxol, arguably the most important anticancer agent against ovarian and breast cancer. In Taxus, taxadiene is directly synthesized from geranylgeranyl diphosphate (GGPP) that is the common precursor for diterpenoids and is found in most plants and microbes. In this study, Artemisia annua L., a Chinese medicinal herb that grows fast and is rich in terpenoids, was used as a genetic engineering host to produce taxadiene. The TXS (taxadiene synthase) gene, cloned from Taxus and inserted into pCAMBIA1304, was transformed into Artemisia annua L. using the Agrobacterium tumefaciens-mediated method. Thirty independent transgenic plants were obtained, and GC-MS analysis was used to confirm that taxadiene was produced and accumulated up to 129.7 μg/g dry mass. However, the high expression of TXS did not affect plant growth or photosynthesis in transgenic Artemisia annua L. It is notable that artemisinin is produced and stored in leaves and most taxadiene accumulated in the stem of transgenic Artemisia annua L., suggesting a new way to produce two important compounds in one transgenic plant: leaves for artemisinin and stem for taxadiene. Overall, this study demonstrates that genetic engineering of the taxane biosynthetic pathway in Artemisia annua L. for the production of taxadiene is feasible.
url http://dx.doi.org/10.1155/2015/504932
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