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<p>Camptothecin (CPT), a monoterpene indole alkaloid with significant anticancer properties, is primarily sourced from <i>Camptotheca acuminata</i>. However, its complex chemical structure and low natural accumulation hinder large-scale clinical applications. To enhance CPT production, this study explored the heterologous expression of <i>CrLAMT</i>, a O-methyltransferase from <i>Catharanthus roseus</i> in <i>C. acuminata</i>. The introduced CrLAMT successfully activated an alternative methylated intermediate pathway in <i>C. acuminata</i>, enabling the conversion of loganic acid to loganin. This dual-pathway approach modification increased CPT content in both leaves and hairy roots, with a 2.23-fold and 1.78-fold increase observed in transgenic materials compared to controls. In addition, <i>CaSTR2</i>, a key downstream enzyme in the CPT biosynthesis pathway, was significantly up-regulated. The study demonstrates that the overexpression of <i>CrLAMT</i> not only enhances CPT production but also optimizes the utilization of intermediate metabolites. This metabolic engineering strategy provides a novel approach to improving the yield of natural products like CPT, and also provides valuable insights for promoting the metabolism of other high value natural products.</p>

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Enhancing camptothecin biosynthesis in Camptotheca acuminata through CrLAMT transfer from Catharanthus roseus

  • 期刊论文

  • 发表日期：

    2026年5月15日

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  • Ru Huang,
  • Wen-Hui Ma,
  • Bing-Run Yang,
  • Fang Yu,
  • Ping Kou

摘要

Camptothecin (CPT), a monoterpene indole alkaloid with significant anticancer properties, is primarily sourced from Camptotheca acuminata. However, its complex chemical structure and low natural accumulation hinder large-scale clinical applications. To enhance CPT production, this study explored the heterologous expression of CrLAMT, a O-methyltransferase from Catharanthus roseus in C. acuminata. The introduced CrLAMT successfully activated an alternative methylated intermediate pathway in C. acuminata, enabling the conversion of loganic acid to loganin. This dual-pathway approach modification increased CPT content in both leaves and hairy roots, with a 2.23-fold and 1.78-fold increase observed in transgenic materials compared to controls. In addition, CaSTR2, a key downstream enzyme in the CPT biosynthesis pathway, was significantly up-regulated. The study demonstrates that the overexpression of CrLAMT not only enhances CPT production but also optimizes the utilization of intermediate metabolites. This metabolic engineering strategy provides a novel approach to improving the yield of natural products like CPT, and also provides valuable insights for promoting the metabolism of other high value natural products.