# Origin and Function of Structural Diversity in the Plant Specialized Metabolome
## 2 The Four Major Specialized Metabolome Pathways
### Phenolics  
Embryophytes, or land plants, appeared in the mid-Paleozoic era, between 480 and 360 million years ago. The successful adaptation of _Charophivaceae_ from living underneath  
Figure 3: Biosynthesis of Alkaloids. the water to living on land was achieved by the production of phenolic compounds, which act as antioxidants in the protection against UV radiation [54]. The classification of phenolics is mainly based on their aromatic skeleton, e.g., C\({}_{6}\)C\({}_{3}\) (phenylpropanoids), C\({}_{6}\)C\({}_{3}\)C\({}_{6}\) (flavonoids) or (C\({}_{6}\)C\({}_{3}\)C\({}_{6}\))\({}_{2}\) (proanthocyanidins, also called condensed tannins) [54]. There are two biosynthetic pathways leading towards phenolic compounds, namely, via polykele biosynthesis which mainly occurs in micro-organisms (Figure 1), and via the shikimate pathway (Figure 4), yielding the aromatic amino acids L-phenylalanine (Phe), L-tyrosine (Tyr) and L-tryptophan (Trp) [55]. The shikimate pathway is employed by both micro-organisms and plants but does not exist in humans; therefore, the aromatic amino acids Phe, Tyr and Trp are essential for humans [56]. The shikimate pathway (Figure 4) starts with the aldol condensation of the glycolytic intermediate phosphoenolpyruvate and erythrose-4-phosphate, which is produced via either photosynthesis or the pentose phosphate pathway, to form 2-dehydro-3-deoxy-arabino-heptulosonate-7-phosphate (DAHP). Next, DAHP is converted to 3-dehydroquinate, which can be reduced to quinate or dehydrated to 3-dehydroshikimate, the latter being the precursor of the benzenoids protocatechuate and gallate [55]. Gallate is, in turn, the starter-molecule for the biosynthesis of hydrolyzable tannins [57]. Via shikimate, 3-dehydroshikimate is converted to chorismate, from which some simple aniline derivates are produced using glutamine as an amino-donor, e.g., \(p\)-aminobenz acid (\(p\)ABA). \(p\)ABA is part of the folic acid (vitamin B\({}_{9}\)) structure, an essential compound in DNA synthesis, methylation and cellular division [58]. Biofortification of maize by boosting folate biosynthesis has been demonstrated as an attractive strategy to enhance the nutritional value of maize [59; 60]. Another aniline derivate, anthranilic acid, is an intermediate in the biosynthetic pathway to the aromatic amino acid Trp, which serves as a precursor for many indolics, for example, indole-3-acetic acid (IAA), a major regulator of plant growth [61]. Isomerization of chorismate to isochorismate is the crucial step in the biosynthesis of the benzenoids, 2,3-dihydroxybenzoate and salicylate (see below). Furthermore, chorismate is an intermediate in the pathway towards the two aromatic amino acids Phe and Tyr. The first step in the biosynthesis of Phe and Tyr involves the conversion of chorismate to prephenate (Figure 4). Then, two alternative pathways are possible. In the first, the arogenate pathway, prephenate, is transaminated to aprogene, followed by a dehydration and decarboxylation to Phe or a dehydration and a decarboxylation to Tyr. In an alternative route, the opposite occurs: prephenate is first dehydrated/dehydrogenated and decarboxylated to phenylpyruvate and \(p\)-hydroxyphenylpyruvate and then transaminated to produce Phe and Tyr [55]. Most microorganisms utilize the phenylpyruvate/\(p\)-hydroxyphenylpyruvate pathways, whereas biosynthesis of Phe and Tyr in plants has been predominantly described to occur via the aprogene pathway [62]. However, the alternative biosynthesis of Phe via phenylpyruvate, with Tyr as the amino-donor, has been described in _Petutia hybrida_ flowers [63]. The and Tyr form the basis for the C\({}_{6}\)C\({}_{3}\) phenylpropane unit that is found in a wide range of phenolic compounds, such as phenylpropanoids, flavonoids, coumarins, monolignols, lignins and lignans [64]. The general phenylpropanol pathway starts with the deamination of Phe leading to _trans_-cinnamate (Figure 5).