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<p>This study first integrates genomic and chemical analyses of <i>Botryosphaeria dothidea</i> isolated from <i>Aquilaria sinensis</i> to investigate its role in agarwood formation. Whole-genome sequencing revealed a 44.33 Mb assembly encoding 69 biosynthetic gene clusters (BGCs). antiSMASH analysis revealed that 37 of these BGCs (53.6%) display no significant similarity to known pathways in the MIBiG database, which is dominated by NRPS-like, T1PKS, and terpene types. Chemical profiling of the fungal fermentation extract led to the identification of ten compounds, including the new 4-hydroxyphenethyl (<i>S</i>)-5-oxofuran-2-carboxylate (<b>1</b>), along with known phenylethanoid derivatives (<b>2</b>, <b>3</b>), cyclic peptides (<b>5</b>-<b>7</b>), and others (<b>4</b>, <b>8</b>–<b>10</b>). Bioassays revealed weak anti-MRSA activity for compounds <b>4</b>, <b>7</b>, <b>9</b>, and <b>10</b>, with ergosterol peroxide (<b>10</b>) additionally showing moderate anti-inflammatory effects (IC<sub>50</sub> = 31.0 <i>μ</i>M) via NO suppression. Genomic and chemical analyses confirmed conserved pathways for metabolites such as ACT-Toxin II and clavaric acid. Notably, the isolated metabolites <b>1</b>–<b>3</b> were found to structurally mimic key precursors of host-derived 2-(2-phenylethyl)chromones (PECs). This structural mimicry suggests a mechanism for host-pathogen crosstalk that potentially triggers defense responses, such as resin accumulation. These findings uncover the genetic and chemical basis of <i>B. dothidea</i>’s role in agarwood formation and provide a foundation for developing artificial induction strategies.</p>

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Genomic and chemical profiling of Botryosphaeria dothidea: cryptic biosynthetic gene clusters and secondary metabolites in agarwood formation

  • 期刊论文

  • 发表日期：

    2025年9月19日

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  • Xiao-Yan Duan,
  • Dong-Bao Hu,
  • Hataichanok Pandith,
  • Terd Disayathanoowat,
  • Xue Bai,
  • Ya-Jun Han,
  • Qing-Hua Kong,
  • Jun Yang,
  • Ji-Feng Luo,
  • Xing-Yu Li,
  • Angkhana Inta,
  • Yue-Hu Wang

摘要

This study first integrates genomic and chemical analyses of Botryosphaeria dothidea isolated from Aquilaria sinensis to investigate its role in agarwood formation. Whole-genome sequencing revealed a 44.33 Mb assembly encoding 69 biosynthetic gene clusters (BGCs). antiSMASH analysis revealed that 37 of these BGCs (53.6%) display no significant similarity to known pathways in the MIBiG database, which is dominated by NRPS-like, T1PKS, and terpene types. Chemical profiling of the fungal fermentation extract led to the identification of ten compounds, including the new 4-hydroxyphenethyl (S)-5-oxofuran-2-carboxylate (1), along with known phenylethanoid derivatives (2, 3), cyclic peptides (5-7), and others (4, 8–10). Bioassays revealed weak anti-MRSA activity for compounds 4, 7, 9, and 10, with ergosterol peroxide (10) additionally showing moderate anti-inflammatory effects (IC50 = 31.0 μM) via NO suppression. Genomic and chemical analyses confirmed conserved pathways for metabolites such as ACT-Toxin II and clavaric acid. Notably, the isolated metabolites 1–3 were found to structurally mimic key precursors of host-derived 2-(2-phenylethyl)chromones (PECs). This structural mimicry suggests a mechanism for host-pathogen crosstalk that potentially triggers defense responses, such as resin accumulation. These findings uncover the genetic and chemical basis of B. dothidea’s role in agarwood formation and provide a foundation for developing artificial induction strategies.