Strategies for enhancing alkaloids yield in catharanthus roseus via metabolic engineering approaches

Abstract

As the only source for the low-abundance antitumor agents vinblastine and vincristine, Catharanthus roseus is highly valued for its diversity of more than 130 monoterpenoid indole alkaloids (MIAs) and has been studied extensively as a model for medicinal plants improvement. However, the low yield increases the cost and limits the industrial production of these valuable MIAs in medical use. The biosynthesis of these MIAs is a complex multistep enzymatic network that is tightly regulated by developmental and environmental factors. Many genes encoding constitutive structural biosynthetic enzymes, transcription factors, and transporters involved in these pathways have been cloned and characterized. To improve the MIA production, a couple of approaches have been carried on the plants, hairy roots, and cell culture of C. Roseus, as well as on heterogeneous plant (like Nicotiana benthamiana), including abiotic and biotic methods. The main strategies for enhancing alkaloids yield is to genetically modify the MIA pathway and enhance the metabolic flux to MIA production via metabolic engineering strategies. Here, we will review the past decades' efforts on the MIA production.