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<p>Celangulin V is a widely used biopesticide derived from <i>Celastrus angulatus</i>, and features antifeedant and insecticidal properties as a dihydro-β-agarofuran (DHβAF) sesquiterpenoid. Its biosynthesis remains largely unexplored. Here, we assemble a chromosome-level and haplotype-resolved reference genome of <i>C. angulatus</i>, with each haplotype assembled into 23 pseudochromosomes and achieving scaffold N50 of 14.31 and 14.01 Mb, respectively. This high-quality genome reveals that a recent <i>β</i> whole-genome triplication (<i>β-</i>WGT) event occurred ~34.3 million years ago, and that the expansion of sesquiterpene synthases and cytochrome P450s from the <i>CYP71BE</i> family results from whole-genome duplication (WGD) event and tandem duplication, respectively. We identify <i>CaTPS16</i> as a γ-eudesmol synthase, and show that <i>CYP71BE416</i> further catalyzes the γ-eudesmol to tetrahydrofuran ring α-agarofuran for Celangulin V biosynthesis. We further achieve the de novo synthesis of α-agarofuran in <i>Saccharomyces cerevisiae</i> through combined coexpression of these genes. This study has significantly increases the available genomic resources of the Celastraceae family, improves our understanding of the biosynthetic origins and evolution of the tetrahydrofuran ring in DHβAF sesquiterpenoids, and enables its heterologous bioproduction in microbial chassis.</p>

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Biosynthesis and heterologous production of the α-agarofuran scaffold of Celangulin V from Celastrus angulatus

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月3日

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  • Weiguo Li,
  • Andong Zhu,
  • Wei Li,
  • Shengli Wang,
  • Dongmei Liang,
  • Xiaoguang Yan,
  • Ruiqi Chen,
  • Daoguang Tian,
  • Ziming Liu,
  • Zhaonong Hu,
  • Shaopeng Wei,
  • Yi Zhang,
  • Mingzhang Wen,
  • Qinggele Caiyin,
  • Jianbin Yan,
  • Jianjun Qiao

摘要

Celangulin V is a widely used biopesticide derived from Celastrus angulatus, and features antifeedant and insecticidal properties as a dihydro-β-agarofuran (DHβAF) sesquiterpenoid. Its biosynthesis remains largely unexplored. Here, we assemble a chromosome-level and haplotype-resolved reference genome of C. angulatus, with each haplotype assembled into 23 pseudochromosomes and achieving scaffold N50 of 14.31 and 14.01 Mb, respectively. This high-quality genome reveals that a recent β whole-genome triplication (β-WGT) event occurred ~34.3 million years ago, and that the expansion of sesquiterpene synthases and cytochrome P450s from the CYP71BE family results from whole-genome duplication (WGD) event and tandem duplication, respectively. We identify CaTPS16 as a γ-eudesmol synthase, and show that CYP71BE416 further catalyzes the γ-eudesmol to tetrahydrofuran ring α-agarofuran for Celangulin V biosynthesis. We further achieve the de novo synthesis of α-agarofuran in Saccharomyces cerevisiae through combined coexpression of these genes. This study has significantly increases the available genomic resources of the Celastraceae family, improves our understanding of the biosynthetic origins and evolution of the tetrahydrofuran ring in DHβAF sesquiterpenoids, and enables its heterologous bioproduction in microbial chassis.