# Biosynthetic Pathways of Hormones in Plants
## 10 Gibberellins  
Gibberellins (GAs) are tetracyclic and diterpenid plant hormones that form a large group of carboxylic acids [153]. GAs are present in all vascular plants and lower plants, such as lycophytes and ferns. GAs are involved in the promotion of organ growth, enhance cell elongation and/or division, and activate most developmental processes (i.e., seed germination, induction of flowering, and maturation) in many plant species [154; 155]. GAs were first isolated from the fungus _Gibberella fujikuroi_ (reclassified as _Fusarium fujikuroi_), which stimulated growth in infected vascular plants. Next, their presence in plants as phytohormes was confirmed in the late 1950s. The system that numbers GAs, starting with GA\({}_{1}\), assigns GAs in order of their discovery and structural characterization [156]. The most well-known and biologically active GAs in plants are GA\({}_{1}\), GA\({}_{3}\), GA\({}_{4}\), and GA\({}_{7}\). There are three structural properties that alter these GAs: the presence of hydroxyl group in C-3\(\beta\), carboxyl group in C-6, and lactone between C-4 and C-10. The 3\(\beta\)-hydroxyl group can be replaced by other functional groups at positions C-2 and/or C-3. However, GA\({}_{5}\) and GA\({}_{6}\) are representatives of bioactive GAs that lack a hydroxyl group at C-3\(\beta\)[153]. The knowledge of GA biosynthesis has developed rapidly in recent years. Quantitative analysis shows that biosynthesis of GAs occurs in actively growing tissues, i.e., young leaves, shoot apices, and flowers. In contrast, there are some reports that indicate that xylem and phloem exudates contain Gas, suggesting the presence of long-distance transportation of these phytohormes in plants [154; 157; 158]. In plants, GAs are formed from GGPP through IPP, which represents the C-5 building moiety involved in the synthesis of terpenoid (isoprenoid) compounds (Figure 7) [155; 159]. In the green tissues of plants, IPP is produced via two pathways: (i) the MVA pathway in the cytoplasm and (ii) the methylerythitol phosphate (MEP) pathway in plastids in two-step reactions. Such a metabolism is ancient and leads to the synthesis of 12,000 natural diterpenoid products in plant tissues. Recent data suggest that this compound is cyclized to the tetracyclic hydrocarbon precursor _ent_-kaurene in plastids by _ent_-copalyl diphosphate, which predominantly occurs through the MEP pathway [157]. However, the MVA pathway may also be involved in the synthesis of isoprenoid intermediates of GGPP and their transport from the cytosol into the plastids [160]. The formation of _ent_-kaurene from GGPP takes place in the stroma of proplastids or in the developing chloroplasts, except those of mature chloroplasts [161]. Ten functional GGPP synthase (GGPPS) genes were discovered in _A. thaliana_. Among these genes, seven encode enzymes were localized in the plastid. However, GGPPS11 is expressed most strongly and constitutively in plants that produce most of the substrate utilized in the biosynthesis of various terpenoids in plastids [162]. In contrast to _A. thaliana_, rice is reported to contain one functional GGPPS that is present in the plastid, which is involved in the biosynthesis of all diterenoid compounds, including _ent_-kaurene, which is a key intermediate involved in the formation of GAs [163]. Firstly, the synthesis of _ent_-kaurene from GGPP starts via cyclization, which initiated by the proton of the dicyclic _ent_-copalyl diphosphate (CPP), which is catalyzed by a type II diterpene cyclase: _ent_-copalyl diphosphate synthase (CPS) (Figure 11). CPS contains a conserved DXDD motif, in which aspartate gives a proton to initiate this reaction via cyclization. Additionally, a water molecule attached to amino acids (histidine and asparagine) plays role as the catalytic base that accepts a proton and terminates the reaction [164]. CPS activity is inhibited by high concentrations of both Mg\({}^{2+}\) and GGPP, which are promoted by light, leading to reduced flux into the GA pathway during de-etiolation.