Advances in Metabolic Engineering of Plant Monoterpene Indole Alkaloids

SIMPLE SUMMARY: Plants produce very diverse chemicals that are used for the treatment of human ailments. However, plants tend to produce these high-value compounds in small amounts. The rapid development of modern synthetic biology tools has facilitated the engineering of living organisms to allow them to manufacture plant natural products. Herein, we highlight the advances of strategies to engineer more robust systems for increased production of plant-based chemicals with medicinal value in non-native systems, including in yeast and tobacco plants. Success in engineering these platforms will ultimately provide more access to plant-based medicines. ABSTRACT: Monoterpene indole alkaloids (MIAs) encompass a diverse family of over 3000 plant natural products with a wide range of medical applications. Further utilizations of these compounds, however, are hampered due to low levels of abundance in their natural sources, causing difficult isolation and complex multi-steps in uneconomical chemical syntheses. Metabolic engineering of MIA biosynthesis in heterologous hosts is attractive, particularly for increasing the yield of natural products of interest and expanding their chemical diversity. Here, we review recent advances and strategies which have been adopted to engineer microbial and plant systems for the purpose of generating MIAs and discuss the current issues and future developments of manufacturing MIAs by synthetic biology approaches.