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

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.