Integrative multi-omics data provide insights into the biosynthesis of furanocoumarins and mechanisms regulating their accumulation in Angelica dahurica

被引:0
作者
Jiaojiao Ji [1 ]
Xiaoxu Han [1 ]
Lanlan Zang [2 ]
Yushan Li [1 ]
Liqun Lin [3 ]
Donghua Hu [1 ]
Shichao Sun [1 ]
Yonglin Ren [4 ]
Garth Maker [1 ]
Zefu Lu [2 ]
Li Wang [2 ]
机构
[1] Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen
[2] College of Environmental and Life Sciences, Murdoch University, Murdoch, WA
[3] Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing
[4] College of Plant Science and Technology, Huazhong Agricultural University, Wuhan
[5] Kunpeng Institute of Modern Agriculture at Foshan 528000, Foshan
基金
中国国家自然科学基金;
关键词
D O I
10.1038/s42003-025-08076-x
中图分类号
学科分类号
摘要
Furocoumarins (FCs), important natural compounds with biodefense roles and pharmacological activities, are notably abundant in medicinal plant Angelica dahurica. However, its accumulation patterns over development stages in FC-enriched tissue, biosynthetic pathways, and regulatory mechanisms in A. dahurica remain elusive. Here, we quantified the concentration dynamics of 17 coumarins across six developmental stages of root and found a gradual decrease in FC concentration as the roots develop. Using a de-novo assembled chromosome-level genome for A. dahurica, we conducted integrative multi-omics analyses to screen out candidate genes to fill in the sole missing step in the biosynthesis of imperatorin and isoimperatorin. This revealed that CYP71AZ18 catalyzes hydroxylation at the C-5 position of psoralen to generate bergaptol, while CYP71AZ19 and CYP83F95 catalyze hydroxylation at the C-8 position to produce xanthotoxol, notably indicating that a single step is catalyzed by two genes from distinct CYP450 subfamilies in this species. CYP71AZ19 originated from a proximal duplication event of CYP71AZ18, specific to A. dahurica, and subsequently underwent neofunctionalization. Accessible chromatin regions (ACRs), especially proximal ACRs, correlated with high gene expression levels, and the three validated genes exhibited strong signals of ACRs, showing the importance of chromosomal accessibility in regulating metabolite biosynthesis. © The Author(s) 2025.
引用
收藏
相关论文
共 100 条
  • [1] Villard C., Et al., A new P450 involved in the furanocoumarin pathway underlies a recent case of convergent evolution, N. Phytol, 231, pp. 1923-1939, (2021)
  • [2] Hussain M.I., Et al., Natural product coumarins: biological and pharmacological perspectives, Biologia, 74, pp. 863-888, (2019)
  • [3] Ortega-Forte E., Et al., COUPY Coumarins as novel mitochondria-targeted photodynamic therapy anticancer agents, J. Med. Chem, 64, pp. 17209-17220, (2021)
  • [4] Han X., Et al., The chromosome-level genome of female ginseng (Angelica sinensis) provides insights into molecular mechanisms and evolution of coumarin biosynthesis, Plant J, 112, pp. 1224-1237, (2022)
  • [5] Munakata R., Et al., Parallel evolution of UbiA superfamily proteins into aromatic O-prenyltransferases in plants, Proc. Natl. Acad. Sci. USA, 118, (2021)
  • [6] Rodrigues J.L., Gomes D., Rodrigues L.R., Challenges in the heterologous production of furanocoumarins in Escherichia coli, Molecules, 27, (2022)
  • [7] Sarker S.D., Nahar L., Progress in the chemistry of naturally occurring coumarins, Prog. Chem. Org. Nat. Prod, 106, pp. 241-304, (2017)
  • [8] Jian X., Et al., Two CYP71AJ enzymes function as psoralen synthase and angelicin synthase in the biosynthesis of furanocoumarins in Peucedanum praeruptorum Dunn, Plant Mol. Biol, 104, pp. 327-337, (2020)
  • [9] Zhang Y., Bai P., Zhuang Y., Liu T., Two O-methyltransferases mediate multiple methylation steps in the biosynthesis of coumarins in Cnidium monnieri, J. Nat. Prod, 85, pp. 2116-2121, (2022)
  • [10] Nelson D.R., Et al., Comparative genomics of rice and Arabidopsis. Analysis of 727 cytochrome P450 genes and pseudogenes from a monocot and a dicot, Plant Physiol, 135, pp. 756-772, (2004)