Biosynthesis and biotechnological production of anti-cancer drug Camptothecin

Camptothecin (CPT) is a kind of modified monoterpene indole alkaloid firstly identified from woody plant Camptotheca acuminata, and its semisynthetic CPT analogs irinothecan and topothecan are clinically used for the treatment of various cancers throughout the world. However, the extraction of CPT from limited natural CPT-producing plant resources couldn't meet the rapidly increasing market need. The development of plant metabolic engineering provides one alternative way to increase CPT yield by genetic manipulation, which relies on in-depth understanding of the CPT biosynthesis pathway. Several attempts have been also made to obtain CPT by biotechnological approaches such as cell suspensions, endophytic fungi, hairy roots, elicitation as well as metabolic engineering in the past decade. Here, recent advances in knowledge of biosynthesis of CPT, gene isolation, molecular regulation, production improvement and biotechnological methods are summarized and future perspectives are also discussed in this review.