title: Engineering isoprenoid biosynthesis in Artemisia annua L. for the production of taxadiene: a key intermediate of taxol.
abstract: 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.
authors.affiliation: Fudan-SJTU-Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China ; Institute of Biotechnology, College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Meiya
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Biotechnology, College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Fudan-SJTU-Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xiangli
authors.initials: X
authors.lastname: Yu
authors.affiliation: Fudan-SJTU-Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Miao
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism; D031172:Artemisia annua / Q000235:genetics / Q000378:metabolism; D004224:Diterpenes / Q000138:chemical synthesis / Q000378:metabolism*; D006801:Humans; D060847:Metabolic Engineering; D017239:Paclitaxel / Q000138:chemical synthesis / Q000378:metabolism*; D018515:Plant Leaves / Q000378:metabolism; D030821:Plants, Genetically Modified / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000737:chemistry / Q000378:metabolism; D013729:Terpenes / Q000138:chemical synthesis / Q000378:metabolism*
chemical_list: D000475:Alkenes; D000970:Antineoplastic Agents; D004224:Diterpenes; D011106:Polyisoprenyl Phosphates; D013729:Terpenes; C093125:taxa-4(5),11(12)diene; C002963:geranylgeranyl pyrophosphate; D017239:Paclitaxel