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<p>Pachymic acid is a key bioactive triterpenoid of <i>Poria cocos</i>, a medicinal fungus widely used in traditional Chinese medicine, and is responsible for its anti-tumor and anti-inflammatory activities. However, its low natural abundance and reliance on pine wood–based cultivation limit large-scale production and therapeutic application. Methyl jasmonate (MeJA) is known to stimulate triterpenoid biosynthesis in plants and fungi. In this study, we treated liquid-cultured <i>Poria cocos</i> mycelia with MeJA and integrated transcriptomic and targeted metabolomic analyses to identify a cytochrome P450 gene, <i>CYP5035</i>, whose expression strongly correlates with pachymic acid accumulation. We then functionally validated <i>CYP5035</i> by heterologous expression in <i>Saccharomyces cerevisiae</i>. Subsequent metabolic engineering of the yeast strain—through redox partner optimization and dynamic flux redirection—significantly enhanced pachymic acid production. Our work not only reveals the molecular basis of MeJA-induced triterpenoid synthesis but also establishes a sustainable microbial platform for the green and efficient production of pachymic acid.</p>

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Multi-omics-guided discovery of CYP5035 enables heterologous production and engineering of pachymic acid in yeast

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月14日

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  • Ceyuan Liu,
  • Chuang Liu,
  • Binbin Shen,
  • Can Zhong,
  • Jing Xie,
  • Mingzhu Zheng,
  • Jian Jin

摘要

Pachymic acid is a key bioactive triterpenoid of Poria cocos, a medicinal fungus widely used in traditional Chinese medicine, and is responsible for its anti-tumor and anti-inflammatory activities. However, its low natural abundance and reliance on pine wood–based cultivation limit large-scale production and therapeutic application. Methyl jasmonate (MeJA) is known to stimulate triterpenoid biosynthesis in plants and fungi. In this study, we treated liquid-cultured Poria cocos mycelia with MeJA and integrated transcriptomic and targeted metabolomic analyses to identify a cytochrome P450 gene, CYP5035, whose expression strongly correlates with pachymic acid accumulation. We then functionally validated CYP5035 by heterologous expression in Saccharomyces cerevisiae. Subsequent metabolic engineering of the yeast strain—through redox partner optimization and dynamic flux redirection—significantly enhanced pachymic acid production. Our work not only reveals the molecular basis of MeJA-induced triterpenoid synthesis but also establishes a sustainable microbial platform for the green and efficient production of pachymic acid.