The terpenoids are the largest class of natural products. Many exciting products are used as flavors, fragrances, spices in the industrial sector and are also used in perfumery and cosmetics. Many terpenoids have biological activities and are also used in medicine. The conventional acetate-mevalonic acid pathway operates mainly in higher plant cytosol and mitochondria. The non-mevalonic acid pathway occurs in the plastid and synthesizes Hemi-, mono-, sesqui-, and diterpenes together with chlorophyll carotenoids phytol tail. Recent developments in terpenoid biosynthesis, an in-depth description of terpene synthases and their phylogenetic analysis, regulation of terpene biosynthesis, and updates of terpenes entered in the clinical studies are thoroughly reviewed in this review paper.
Background about Terpenes
Plants produce different types of secondary metabolites, many of which were subsequently exploited by humans in a diverse array of biological functions for their beneficial roles (Balandrin et al . 1985). Some terpenoids have their functions in plant defense against biotic and abiotic stress or are used as signal molecules to attract pollination insects. Some have pharmacological and biological activities out of the examined terpenoids and are, therefore, important for medicine and biotechnology. C5 unit generation, such as isopentenyl diphosphate (IPP) or dimethylallyl diphosphate (DMAPP), is the first step of terpenoid biosynthesis. Two separate pathways that can generate the C5 unit were investigated for this study: the pathway of mevalonate and methylerythritol phosphate (MEP). Terpenoids can be graded as C5 (hemiterpenes), C10 (monoterpenes), C15 (sesquiterpenes), C20 (diterpenes), C25 (sesquiterpenes), C30 (triterpenes), C40 (tetraterpenes), > C40 (polyterpenes) on the basis of C5 units (Ashour et al . 2010; Martin et al . 2003).
Terpene synthases are responsible for terpene synthesis and can easily acquire new catalytic properties through minor structural changes (Keeling et al . 2008). Monoterpenes synthesis is initiated by dephosphorylation and ionization of geranyl diphosphate to geranyl carbocation (Huang et al. 2010). Sesquiterpene synthesis begins with the ionization of farnesyl diphosphate to farnesyl cation, which can also be isomerized to nerolidol cation (Degenhardt et al. 2009). Diterpenes are synthesized in two different ways by diterpene synthases. One way is through the ionization of diphosphate, as catalyzed by class I enzyme, and the other through the substrate’s protonation at the 14, 15-double bond of geranyl diphosphate. The non-steroidal triterpenoids are produced by converting squalene into oxidosqualene and cyclization through the formation of dammarenyl cation. Many terpenoids also possess pharmaceutical characteristics and are currently used in clinical practice. Taxus buccal (diterpene) and artemisinin (sesquiterpene lactone) from Artemisia annua are well-known antineoplastic and antimalarial agents among those terpenoids (Croteau et al. 2006; Pollier et al. 2011).
This review deals with terpenoid biosynthesis, terpene synthase phylogeny, terpene biosynthesis regulation, and terpenoid clinical trials. The study highlights the latest approaches to terpene synthase phylogenetic analysis and terpenoid control.
Terpenoids are essential for plants’ survival, and they also possess biological and pharmacological properties that benefit humans. Two compartmentalized pathways can be used in plants to synthesize isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). The terpenoid biosynthesis mevalonic acid pathway acts in cytosol, endoplasmic reticulum, and peroxisomes (Carrie et al . 2007; Hemmerlin et al . 2003; Dudareva et al . 2006; Leivar et al . 2005; Merret et al . 2007; Sapir-Mir et al . 2008; Simkin et al. 2011; Lange and Ahkami 2013). The condensation of three acetyl CoA units leads to the synthesis of 3-hydroxy-3-methylglutaryl CoA, which produces mevalonic acid later on. The mevalonic acid is converted through the phosphorylation and decarboxylation process into isopentenyl diphosphate. 3-hydroxy-3-methylglutaryl CoA reductase catalyzes the reduction to mevalonic acid of 3-hydroxy-3-methylglutaryl CoA (Luskey and Stevens, 1985; Basson et al . , 1988; Igual et al . , 1992; Rodwell, 2000). In Arabidopsis thaliana, mevalonate-5-diphosphate is produced by phosphorylation from mevalonic acid, and mevalonate kinase and phosphomevalonate kinase catalyze the entire reaction (Tsay and Robinson 1991; Lluch et al . 2000). Later, decarboxylase mevalonate-5-diphosphate catalyzes the conversion of mevalonate-5-diphosphate to isopentenyl diphosphate, which results from the terpenoid biosynthesis mevalonic acid pathway (Dhe-Paganon et al . 1994) (Fig . 1).