Bioproduction of terpenoid indole alkaloids from Catharanthus roseus cell cultures

Abstract

Catharanthus roseus is an ornamental plant belonging to the Apocynaceae family which produces flowers of different color for most of the year. Besides its importance as an ornamental plant, its interest today is centered on its capacity to biosynthesize a great variety of terpenoid indole alkaloids (TIAs), which have a high added value due to their wide spectrum of pharmaceutical applications. The most important TIAs are the two antitumoral alkaloids, vinblastine and vincristine. Likewise, C. roseus also produces ajmalicine used as antihypertensive and serpentine used as sedative. The high cost of these alkaloids is due to the very small amounts that occur in C. roseus and the difficulty of their extraction which is carried out in the presence of many other compounds. This problem has created the need to find alternative sources to produce these compounds. In this respect, plant tissue/cell cultures could be a useful alternative source of pharmacologically active C. roseus alkaloids, but, even so, these have only been obtained in very low concentrations and after a substantial amount of research. This problem has stimulated intense research into the biosynthesis of TIAs and in the regulation of its pathways, with the aim of increasing the production of these high-value compounds by biotechnological approaches. The aim of this chapter is centered on different strategies to improve TIA production which have been developed, including screening and selection of high-yield cell lines, optimization of culture conditions, feeding and elicitation strategies, and the metabolic engineering of TIA biosynthetic pathway. An up-to-date view on the biosynthesis of TIAS is also given. Although not yet successful, metabolic engineering offers the most promising perspective for improving TIA production in the future, as increases the knowledge of the genetic determination and regulation of the TIA pathway.