Functional analysis of CYP71AV1 reveals the evolutionary landscape of artemisinin biosynthesis
文献类型：期刊论文
| 作者 | Chen, Fang-Yan4,5; Mu, Qiu-Yan3; Xu, Bing-Yi2,3; Lei, Yu-Chen1,3; Liu, Hui-Ying3; Fang, Xin3 |
| 刊名 | FRONTIERS IN PLANT SCIENCE
 |
| 出版日期 | 2024-03-21 |
| 卷号 | 15页码:9 |
| 关键词 | artemisinin Asteraceae sesquiterpene lactone cytochrome P450 monooxygenases amorpha-4 11-diene oxidase germacrene A oxidase molecular evolution loss-of-function event |
| ISSN号 | 1664-462X |
| DOI | 10.3389/fpls.2024.1361959 |
| 通讯作者 | Fang, Xin(xinfang@mail.kib.ac.cn) |
| 英文摘要 | Artemisinin biosynthesis, unique to Artemisia annua, is suggested to have evolved from the ancestral costunolide biosynthetic pathway commonly found in the Asteraceae family. However, the evolutionary landscape of this process is not fully understood. The first oxidase in artemisinin biosynthesis, CYP71AV1, also known as amorpha-4,11-diene oxidase (AMO), has specialized from ancestral germacrene A oxidases (GAOs). Unlike GAO, which exhibits catalytic promiscuity toward amorpha-4,11-diene, the natural substrate of AMO, AMO has lost its ancestral activity on germacrene A. Previous studies have suggested that the loss of the GAO copy in A. annua is responsible for the abolishment of the costunolide pathway. In the genome of A. annua, there are two copies of AMO, each of which has been reported to be responsible for the different product profiles of high- and low-artemisinin production chemotypes. Through analysis of their tissue-specific expression and comparison of their sequences with those of other GAOs, it was discovered that one copy of AMO (AMOHAP) exhibits a different transcript compared to the reported artemisinin biosynthetic genes and shows more sequence similarity to other GAOs in the catalytic regions. Furthermore, in a subsequent in vitro enzymatic assay, the recombinant protein of AMOHAP unequivocally demonstrated GAO activity. This result clearly indicates that AMOHAP is a GAO rather than an AMO and that its promiscuous activity on amorpha-4,11-diene has led to its misidentification as an AMO in previous studies. In addition, the divergent expression pattern of AMOHAP compared to that of the upstream germacrene A synthase may have contributed to the abolishment of costunolide biosynthesis in A. annua. Our findings reveal a complex evolutionary landscape in which the emergence of a new metabolic pathway replaces an ancestral one. |
| WOS关键词 | AMORPHA-4,11-DIENE SYNTHASE ; MOLECULAR-CLONING ; EXPRESSION ; ANNUA ; CYTOCHROME-P450 ; IDENTIFICATION ; GERMACRENE ; GENES ; P450S ; LESS |
| 资助项目 | National Natural Science Foundation of China[31872666] ; National Key R&D Program of China[2018YFA0900600] ; Yunnan Revitalization Talent Support Program Top Team Project[202305AT350001] ; Young Academic and Technical Leader Raising Foundation of Yunnan Province[201905C160045] ; Key Project at Central Government Level: the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources[2060302] |
| WOS研究方向 | Plant Sciences |
| 语种 | 英语 |
| WOS记录号 | WOS:001196176100001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310529]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Fang, Xin |
| 作者单位 | 1.Yunnan Univ, Sch Chem Sci & Technol, Kunming, Peoples R China 2.Yunnan Univ, Sch Life Sci, Kunming, Yunnan, Peoples R China 3.Kunming Inst Bot, Chinese Acad Sci, State Key Lab Phytochemistry & Plant Resources Wes, Kunming, Peoples R China 4.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China 5.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Fang-Yan,Mu, Qiu-Yan,Xu, Bing-Yi,et al. Functional analysis of CYP71AV1 reveals the evolutionary landscape of artemisinin biosynthesis[J]. FRONTIERS IN PLANT SCIENCE,2024,15:9. |
| APA | Chen, Fang-Yan,Mu, Qiu-Yan,Xu, Bing-Yi,Lei, Yu-Chen,Liu, Hui-Ying,&Fang, Xin.(2024).Functional analysis of CYP71AV1 reveals the evolutionary landscape of artemisinin biosynthesis.FRONTIERS IN PLANT SCIENCE,15,9. |
| MLA | Chen, Fang-Yan,et al."Functional analysis of CYP71AV1 reveals the evolutionary landscape of artemisinin biosynthesis".FRONTIERS IN PLANT SCIENCE 15(2024):9. |
入库方式： OAI收割
来源：上海药物研究所
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