# State-of-the-Art and Opportunities for Bioactive Pentacyclic Triterpenes from Native Mexican Plants
### General Overview of Pentacyclic Triterpenes
#### 1.1.2 Biosynthesis  
The isoprene units integrating triterpenenes are biosynthesized by two metabolic pathways: the mevalonate (MVA) pathway and the 2-C-methyl-D-erythitol-phosphate (MEP) pathway. The MVA pathway occurs in the cytosol from pyruvate and glyceraldehyde 3-phosphate while the MEP pathway occurs in the plastids [19] from 3 acetyl-CoA molecules [20]. The objective of both routes is to produce IPP (isopentenyl diphosphate), a molecule that contains the required isoprene backbone for terpenoid synthesis (Figure 2). On its part, this backbone can be transported between plastids and the cytosol, enabling interactions between both routes [21]. IPP is isomerized to dimethylallyl diphosphate (DMAPP), and this isomer is condensed with another molecule of IPP to produce geranyl diphosphate (GPP), a compound of 10 carbons. If another IPP molecule is added to GPP, farnesyl diphosphate (FPP) with 15 carbons is obtained. The subsequent addition of an IPP unit generates the 20-carbon geranylgeranyl diphosphate (GGPP). These building blocks are the precursor structures of the different terpene groups [22]. The combination of two FPP units through the squalene synthase enzyme forms squalene (30 carbons). In the next step, squalene is turned into squalene epoxide (2,3-oxidosqualene) by squalene monoxigenase and the latter is cyclized with a subsequent structure rearrangement [11; 23], which can be turned into a variety of polycyclic triterpenes depending on the enzymes involved, called oxidosqualene cyclases (OSCs) [24]. However, prior to the action of OSCs, the 2,3-oxidosqualene must adopt a chair-chair (CCC) conformation, with this being a key step in which the synthesis is oriented towards triterpenes, having the dammarenyl cation as an initial intermediate. Otherwise, if the 2,3-oxidosqualene adopts a chair-boat-chair (CBC) conformation, the synthesis is directed to sterols through the protosteryl cation as the main intermediary [23]. Recently, this dichotomy has been questioned because a mutant rice OSC (which normally produces a sterol) yielded a novel PCT with an architecture that is more related to the dammarenyl cation or even to an undescribed third cation [25]. Considering the formation of PTCs from the CCC conformation, OSCs start the cyclization with the protonation of the final double bond in the 2,3-oxidosqualene. The variation in carbocation cyclization and backbone rearrangements generate the diverse groups of PTCs [23; 26]. So, the dammarenyl cation can be expanded from C20 to C18, forming a baccharenyl cation. Another ring expansion to C20 generates a compound of five rings known as the lupyl cation [27], which is the backbone of the lupane group. When the E ring in the lupyl cation suffers an expansion and the carbocation migrates to C19, the germanicyl cation is formed. From this intermediary, the cation re-location to C14 and a methyl shift produces the precursor of usanes. Additionally, the oleanyl cation is rendered from the germanicyl cation, containing the C13 cation in the same way as the ursanyl cation but with two methyl groups in the C20 position instead of a methyl group in C19 and another in C20. The next biosynthesized backbone intermediary from the oleanyl cation is the taraxeryl cation with the cation in C14. If the carbocation migrates to C8, the multiflorenyl cation is produced. When the carbocation is in C9 or C10, the Walsurenyl or companyl cations are produced, respectively. The displacement to the C5 results in a glutinyl cation. Finally, the last PCT and most rearranged (friedelanes) group is formed through the friedely cation with the carbocation in the C4 position (Figure 2). OSCs are encoded by many genes in plants and many of these enzymes may participate in the formation of multiple products [23]. The structure diversification in these groups of PCTs is achieved by modifications of each scaffold base such as oxygenation (i.e., addition of functional groups carbonyl, aldehydl, hydroxyl, carboxyl, and epoxy groups), glycosylation, and acylation.