Engineering Catharanthus roseus monoterpenoid indole alkaloid pathway in yeast

Catharanthus roseus (Madagascar periwinkle), a medicinal plant possessing high pharmacological attributes, is widely recognized for the biosynthesis of anticancer monoterpenoid indole alkaloids (MIAs) - vinblastine and vincristine. The plant is known to biosynthesize more than 130 different bioactive MIAs, highly acclaimed in traditional and modern medicinal therapies. The MIA biosynthesis is strictly regulated at developmental and spatial-temporal stages and requires a well-defined cellular and sub-cellular compartmentation for completion of the entire MIAs biosynthesis. However, due to their cytotoxic nature, the production of vinblastine and vincristine occurs in low concentrations in planta and the absence of chemical synthesis alternatives projects a huge gap in demand and supply, leading to high market price. With research investigations spanning more than four decades, plant tissue culture and metabolic engineering (ME)-based studies were attempted to explore, understand, explain, improve and enhance the MIA biosynthesis using homologous and heterologous systems. Presently, metabolic engineering and synthetic biology are the two powerful tools that are contributing majorly in elucidating MIA biosynthesis. This review concentrates mainly on the efforts made through metabolic engineering of MIAs in heterologous microbial factories. KEY POINTS: • Yeast engineering provides alternative production source of phytomolecules • Yeast engineering also helps to discover missing plant pathway enzymes and genes.