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Functional analysis of CYP71AV1 reveals the evolutionary landscape of artemisinin biosynthesis
Chen, Fang-Yan; Mu, Qiu-Yan; Xu, Bing-Yi; Lei, Yu-Chen; Liu, Hui-Ying; Fang, Xin
2024
发表期刊FRONTIERS IN PLANT SCIENCE
ISSN1664-462X
卷号15页码:1361959
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.
DOI10.3389/fpls.2024.1361959
WOS记录号WOS:001196176100001
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文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/75828
专题中国科学院昆明植物研究所
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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,2024,15:1361959.
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,15,1361959.
MLA Chen, Fang-Yan,et al."Functional analysis of CYP71AV1 reveals the evolutionary landscape of artemisinin biosynthesis".FRONTIERS IN PLANT SCIENCE 15(2024):1361959.
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