Chemoproteomics reveals the epoxidase enzyme for the biosynthesis of camptothecin precursor strictosamide epoxide

Abstract Camptothecin and its derivatives are the third largest anticancer drugs in the world market, mainly used to treat malignant tumors such as lung, colon and cervical cancer. Camptothecin was firstly discovered in Camptotheca acuminate and extracted mainly from C. acuminate and Nothapodytes nimmoniana for medicine production (Sadre et al. 2016). However, the overharvesting of C. acuminate and N. nimmoniana has greatly reduced their populations in nature, which are currently listed as the second protected plants in China and India. It is estimated there would be 20 million new cancer cases in 2025 all over the world, meeting the growing demand for camptothecin and other anti-cancer drugs has become a daunting challenge (Seca et al. 2018). In this study we tried to elucidate the unknown biosynthetic pathway from strictosamide 1 to strictosamide epoxide 2 by unearthing the candidate enzymes from the proteome of plant Ophiorrhiza pumila using the chemoproteomic strategy.