Research progress on the biosynthesis and metabolic engineering of the anti-cancer drug camptothecin in Camptotheca acuminate

Camptothecin (CPT), a well-known natural anti-cancer drug, is produced from woody plant Camptotheca acuminata. Up to now, two CPT-derivatives, irinotecan and topotecan, have been used to treat various cancers all over the world, and more than a dozen camptothecin analogues are in different stages of clinical research and development. The source of camptothecin mainly depends on the extraction from the fruits and barks of C. acuminata to meet the huge clinical demand, which undoubtedly increases the logging of this CPT-producing plant resource. Therefore, it is crucial to improve the content of camptothecin in C. acuminata using metabolic engineering strategies for the sustainable development of medicinal source plants. The camptothecin biosynthesis pathway is complex and only the functional genes that catalyze the biosynthesis of central intermediate strictosidinic acid and CPT-derivatives have been partially resolved. Thus, this review mainly summarized the anti-tumor mechanism and application of camptothecin drugs, the tissue differential distribution and extraction of camptothecin, the biosynthetic genes of camptothecin and its derivatives in C. acuminate. In addition, the application of camptothecin metabolic engineering in CPT-producing plants was also prospected. This review provided assistance for increasing camptothecin content and C. acuminata germplasm innovation using camptothecin metabolic engineering technologies.