Plant cell biofactories as in vitro production platforms of the anticancer drug camptothecin

Plants have been a treasure trove for products traditionally used in healthcare from time immemorial. Their contribution to the pharmaceutical, nutraceutical, and chemotherapeutic armamentarium has been unequivocally significant. Plant products, specifically secondary metabolites, have been under the limelight for their extensive use in the pharmaceutical industry with a plethora of applications ranging from treating deadly diseases like cancer to minor ones such as common cold. Camptothecin, an anticancer drug, was first identified and isolated from Camptotheca acuminata, a medicinal tree of China. The chief function of the metabolite in planta is to offer protection against herbivores. It acts on the replicating fork of DNA-topoisomerase I complex and inhibits their dissociation further arresting the cell division and cancer growth. Apart from anticancerous activity, camptothecin possesses antiviral, antifungal, and anti-parasitic activity. So far, camptothecin has been commercially extracted only from trees, C. acuminata and Nothapodytes nimmoniana (native to Indo-China region). However, the quantity of camptothecin present in these trees is subjected to seasonal and geographic variations. Furthermore, due to high demand of camptothecin, extraction from natural sources has led to significant decrease in the number of trees in their natural habitat and adulteration of the raw material during collection. Chemical synthesis of camptothecin has its own limitations such as high cost, harsh chemical and physical reaction conditions, low product yield, and tedious downstream processing. As a promising alternative, in vitro plant cell/tissue culture technology may be utilized to achieve a large-scale production of camptothecin for sustainable and continuous production to meet the ever-increasing market demand. Thus, apart from an overview of camptothecin discovery, structure, and mechanism of action, this chapter aims to highlight and discuss the current developments in bioprocess optimization and metabolic engineering strategies culminated with a discussion on bioreactor design for the in vitro production of camptothecin via plant cell biofactories.