Metabolic Engineering & Synthetic Biology of Monoterpenoid Indole Alkaloids Pathway in Catharanthus Roseus

Abstract

The anti-neoplastic herb, Catharanthus roseus (L.) G. Don (Apocynaceae), is a high-value, low-volume medicinal herb, which is the focus of global attention in view of being the source of terpenoid indole alkaloids (MIAs). MIAs are one of the largest classes of phyto-alkaloids, and many of them are sources of important pharmaceutical products. C. roseus is known to harbour more than 130 different bioactive MIAs that make it an interesting plant, finding use in several traditional and modern medical therapies. The remarkable presence of cellular and subcellular compartmentations for the synthesis and storage of MIAs allows the accumulation of these medicinally important MIAs in leaves (viz. vindoline, catharanthine, vinblastine, vincristine) and stem and roots (viz. tabersonine, ajmalicine, reserpine, serpentine, vindoline, catharanthine, horhammericine, leurosine, lochnerine). Out of them, any medicinally active MIAs found in Catharanthus roseus, vinblastine and vincristine are special since they possess anticancerous properties, along with ajmalicine and serpentine, which possess antihypertensive properties. However, the low plant yield and nonavailability of alternative chemical synthesis methods have increased their demand and market cost. In the research era of more than three decades, a plethora of studies have been carried out on C. roseus to explore, understand, explain, improve and enhance the Homo/Heterologous biosynthesis of MIAs. Metabolic engineering (ME) and synthetic biology are two powerful tools that have played and contributed majorly to MIAs studies. This chapter concentrates mainly on the efforts made through metabolic engineering and synthetic biology of MIAs in plant and microbial factories in the last three decades.