## 1 Introduction  
Isoprenoids, also called terpenoids, constitute a large and highly diverse family of natural products, comprising circa 30,000 distinct compounds in plants. Besides being essential components of the primary metabolism acting as photosynthetic pigments, hormones or redox cofactors, isoprenoids also include specialized metabolites involved in pollinator attraction as well as plant defense against pathogens and herbivores [1; 2] Among the defensive terpenoids, plants from the Apocynaceae, Nyssaceae, Loganiaceae, and Rubiaceae families especially synthesize monoterpene indole alkaloids (MIAs) for which more than 2500 distinct structures have been described so far [3; 4]. For instance, the Madagascar periwinkle (_Catharantthus roseus_) accumulates more than 130 different MIAs, which limit organ consumption or cause aggressor intoxication upon feeding [5; 6; 7]. This cytotoxicity also confers highly valuable pharmaceutical properties to several prominent MIAs, such as the antineoplastic vinblastine and vincristine accumulated in _C. roseus_. The high economic value of these two compounds has thus prompted many research groups to elucidate MIA biosynthetic pathways in Apocynaceae, making _C. roseus_ a model nonmodel plant [8]. This ultimately led to the characterization of the last steps of vindoline and catharanthine synthesis, the two precursors of vinblastine and vincristine [9; 10; 11; 12; 13]. These recent works represent essential advances with a view toward considering the biotechnological production of some interesting MIAs by heterologous hosts [14; 15; 16]. MIAs exhibit a complex biosynthetic pathway with almost all MIA being derived from strictosidine, which is considered as the first MIA [17]. While multiple decorations and cyclizations of strictosidine yield the plethora of MIAs, its synthesis always starts with the condensation of the indole precursor tryptamine with the monoterpene secoiridoid precursor secologanin. Tryptamine is a shikimate-derived product generated through a single enzymatic step of tryptophan decarboxylation [18]. Secologanin biosynthesis is a more intricate process relying on a nine-step conversion of geranyl diphosphate (GPP), named monoterpene seco-iridoid (MSI) pathway and involving distinct enzyme isoforms [19; 20]. Interestingly, the GPP pool engaged in MIA synthesis exclusively comes from the 2C-methyl-D-erythnitol 4-phosphate (MEP) pathway [21]. The MEP pathway produces both isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) through seven enzymatic reactions initiated by the synthesis of 1-deoxy-D-xylulose 5-phosphate (DXP) from pyruvate and glyceraldehyde 3-phosphate (Figure 1). This reaction is catalyzed by DXP synthase (DXS), encoded by a small gene family in higher plants [22; 23; 24]. The DXS isopenes have been clustered into two related gene groups: Clade I-DXS including housekeeping genes [25] and Clade II-DXS including genes associated with plant defense and secondary metabolism [23; 26]. DXP is then sequentially converted into MEP by DXP reductoisomerase (DXR) and into 4-(cytidine 5'diphospho)-2-C-methyl-D-erythnitol (CDP-ME) following the addition of cytidine triphosphate by CDP-ME synthase (CMS). Figure 1: The 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway yielding isopentenyl diphosphate (IPP) and its allylic isomer dimethylallyl diphosphate (DMAPP). DXS, 1-deoxy-D-xylulose 5-phosphate synthase; DXR, 1-deoxy-D-xylulose 5-phosphate reductase; CMS, 2-C-methyl-D-erythritol 4-phosphate synthase; CMK, 4-(cytidine 5’diphospho)-2-C-methyl-D-erythritol kinase; MECS, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; HDS, (_E_)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase; HDR, (_E_)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase; IDI, isopentenyl diphosphate isomerase. DXS2.1 and DXS2.2 correspond to class II DXS isoforms. cDNA characterized in this work are underlined.