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<p>Furocoumarins (FCs), important natural compounds with biodefense roles and pharmacological activities, are notably abundant in medicinal plant <i>Angelica dahurica</i>. However, its accumulation patterns over development stages in FC-enriched tissue, biosynthetic pathways, and regulatory mechanisms in <i>A. dahurica</i> 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 <i>A. dahurica</i>, 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 <i>C</i>-5 position of psoralen to generate bergaptol, while CYP71AZ19 and CYP83F95 catalyze hydroxylation at the <i>C</i>-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 <i>A. dahurica</i>, 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月23日

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  • Jiaojiao Ji,
  • Xiaoxu Han,
  • Lanlan Zang,
  • Yushan Li,
  • Liqun Lin,
  • Donghua Hu,
  • Shichao Sun,
  • Yonglin Ren,
  • Garth Maker,
  • Zefu Lu,
  • Li Wang

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.