Go with the flow: The subcellular compartmentalization of enzymatic interactions for Monoterpene Indole Alkaloid biosynthesis in Catharanthus roseus

Abstract

Vinblastine is an important chemotherapeutic drug classified as a monoterpene indole alkaloid (MIA). While its naturally produced by complex biosynthetic pathways in the flowering plant Catharanthus roseus, its supply for commercial pharmaceuticals is limited by low yields. Synthetic chemical synthesis is inefficient due to the structural complexity of MIAs, and natural abundance is low. Although recent advances have enabled de novo biosynthesis of vinblastine precursors in yeast, yields remain insufficient for commercial viability. A central question that remains in the field is how plants are organizing these biochemical reactions spatially. In this study, I use bimolecular fluorescence complementation (BiFC) assays in Nicotiana benthamiana epidermal leaf cells to investigate protein-protein interactions between C. roseus enzymes in the vinblastine pathway and their subcellular localization. These findings deepen our understanding of the MIA biosynthesis spatial organization and provide insights into the pathway enzyme interactions; ultimately informing targeted bioengineering strategies to enhance therapeutic MIA production in heterologous systems.