Press for MIA production! The role of the Rho of plant GTPases in plant-specialized metabolism

Plants are the most sophisticated biofactories in nature, capable of synthesizing highly valuable compounds of industrial, pharmaceutical, or cosmetic interest.The tropical plant Catharanthus roseus, commonly known as Madagascar Periwinkle, is highly appreciated, not only for its ornamental beauty but also for being a source of specialized metabolites with therapeutic properties called monoterpene indole alkaloids (MIA).Some examples include anticancer compounds, vinblastine and vincristine (Dhyani et al., 2022), or ajmalicine and serpentine which are used in the treatment of hypertension (Kostin et al., 1986).The biosynthesis of MIAs is a highly intricate process, involving over 50 enzymes from various pathways, transcription factors (TFs), intra-/intercellular signaling molecules, and transporters (Pan et al., 2016).Regulation of MIA biosynthesis is complex and likely involves post-translational modifications (PTM) acting as molecular switches to modulate metabolic processes (Friso and van Wijk, 2015).Geranylgeranylation is a PTM carried out by geranylgeranyltransferase (PGGT) that attaches a C20 geranylgeranyl lipid moiety to the target protein (Crowell and Huizinga, 2009).Kumar et al., 2020 showed that both the silencing and overexpression of CrPGGT-I_β or geranylgeranyl diphosphate synthase 2 (CrGGPPS2), responsible for providing the geranylgeranyl moiety to CrPGGT-I_β, resulted in respective decreases and increases in MIA biosynthesis in C. roseus.These findings underscore the importance of geranylgeranylation in MIA production, however, the specific targets of protein geranylgeranylation and its role in modulating specialized metabolism remain unknown.