**1. Introduction**

Flavonoids, are the largest class of secondary metabolites, having polyphenolic structure, which widely distributed in several parts as leaves, root, stem, bark, fruit, flower, weed, of diverse plant species [1]. The flavonoids play a key role to provide pigments in plant as dark blue and red color of berries, yellow and orange color of citrus fruits. These flavonoids play similar role as vitamins in the human body [2]. The flavonoids are constituted by 15 carbon atoms, which are arranged in C6-C3-C6 backbone skeleton rings, in which ring A and ring B are linked by three carbon ring C [3]. The skeleton of ring represented in **Figure 1**.

On the basis of substitution pattern, flavonoids can be classified into major subgroups as chalcone, flavanone, dihydroflavonol, flavanol, flavones, isoflavone, flavonol, leucoanthocyanidin, proanthocyanidin (condensed tannins), anthocyanin [4]. The nature of these flavonoids depends on the basis of degree of hydroxylation, structural class, conjugations, substitutions and degree of polymerization [5]. Approximately, 9000 diverse type flavonoids have been reported and sure this number will be increased [6]. The diverse type flavonoids show diverse biological function as protection from UV radiation, apoptosis,

**Figure 1.** *Basic skeleton C6-C3-C6 of ring A, B, and C in flavonoids.*

treatment of psoriasis [7, 8]. The diverse class of flavonoids have been isolated from several plant species as quercetin and apigenin from *Cymbopogon citratus* [9], pinostrobin and cardamonin chalcone from rhizomes of *Boesenbergia rotunda* [10], 6-aldehydo-isoophiopogonanone A, 6-aldehydo-isoophiopogonanone B, methylophiopogonanone A and methylophiopogonanone B from fibrous roots of *Ophiopogon japonicus* [11]. The diverse type flavonoids were synthesized in plant species via shikimate and phenylpropanoid pathway. Several types enzyme as DAHP synthase, DHQ synthase, SA kinase, PAT, ADT, 4CL, CHS, CHI, F3H, DFR play key role in the biosynthesis of flavonoids [12, 13].

## **2. Shikimate pathway**

Shikimate pathway plays high potential role in the biosynthesis of flavonoids. Several key enzymes are involved in this pathway for biosynthesis of shikimic acid. This pathway starts with the aldol condensation reaction of phosphoenol pyruvate (PEP) and D-erythrose 4-phosphate (E4P) to generate seven carbon keto acid, 3-deoxy-D-arabino-heptulosonate −7-phosphate (DAHP). This reaction catalyzes by 3-deoxy-D-arabino-heptulosonate −7-phosphate synthase (DAHPS) enzyme. The DAHPS is a highly potential enzyme of the shikimate pathway. Two DAHPS genes as DHS1 and DHS2 are found in *Arabidopsis thaliana* plants [14]. From literature, it is identified that DHS1 is more produced by infiltration or by physical wounding with pathogen in both tomato and Arabidopsis [15]. The DAHP is transformed to 3-dehydroquinic acid (DHQ ) by intramolecular cyclization reaction in presence of DHQ synthase enzymes.

In most bacteria, DHQS is monofunctional and in some organism, it behaves multifunctional enzyme, which catalyze 2, 3, 4, and 5 steps of the shikimate pathway. The DHQS is a small part of larger AROM protein, which is pentafunctional peptide containing enzyme [16, 17]. The *Neurospora crassa* and *Aspergillus nidulans* DHQS enzyme found in nature as part of the AROM protein [18]. The DHQ converts into 3-dehydroshikimic acid (DHS) by losing a water molecule.

In the fourth step, DHS is transformed into shikimic acid by removing water molecule. The phosphorylation of shikimic acid is done by activating of shikimate kinase enzyme in the fifth step reaction. The shikimic acid with ATP is phosphorylated at the 5-OH group of shikimic acid converts into shikimic acid 3-phosphate (S3P). The shikimate kinase enzyme is not found in the human cell, but is an essential enzyme of many bacterial pathogens [19, 20]. The shikimic acid 3-phosphate converts into 3-enolpyruvyl shikimate −5-P (EPSP) by EPSP synthase enzymes.

The EPSPS is activating of shikimic acid 3-phosphate in the sixth step reaction of the shikimate pathway. According to intrinsic glyphosate sensitivity, it enzyme has been classified as a class I EPSP synthases and class II EPSP synthases [21, 22].

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**Figure 2.**

*Shikimate pathway in biosynthesis of flavonoids.*

*Biosynthesis of Diverse Class Flavonoids* via *Shikimate and Phenylpropanoid Pathway*

chorismic acid (CHA) by eliminating of the pi group at C-3.

The class I EPSP synthases are found in plant and some bacteria as *Escherichia coli* and *Salmonella typhimurium*. The class II EPSP synthases is found several bacteria species as *Streptococcus pneumonia*, *Streptococcus aureus*. The EPSP converts into

The end product of shikimate pathway is chorismic acid, which found in plants, fungi, bacteria and some parasites [23]. The chorismate synthases (CS) is divided

*DOI: http://dx.doi.org/10.5772/intechopen.96512*

*Biosynthesis of Diverse Class Flavonoids* via *Shikimate and Phenylpropanoid Pathway DOI: http://dx.doi.org/10.5772/intechopen.96512*

The class I EPSP synthases are found in plant and some bacteria as *Escherichia coli* and *Salmonella typhimurium*. The class II EPSP synthases is found several bacteria species as *Streptococcus pneumonia*, *Streptococcus aureus*. The EPSP converts into chorismic acid (CHA) by eliminating of the pi group at C-3.

The end product of shikimate pathway is chorismic acid, which found in plants, fungi, bacteria and some parasites [23]. The chorismate synthases (CS) is divided

**Figure 2.** *Shikimate pathway in biosynthesis of flavonoids.*

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

play key role in the biosynthesis of flavonoids [12, 13].

*Basic skeleton C6-C3-C6 of ring A, B, and C in flavonoids.*

**2. Shikimate pathway**

**Figure 1.**

in presence of DHQ synthase enzymes.

treatment of psoriasis [7, 8]. The diverse class of flavonoids have been isolated from several plant species as quercetin and apigenin from *Cymbopogon citratus* [9], pinostrobin and cardamonin chalcone from rhizomes of *Boesenbergia rotunda* [10], 6-aldehydo-isoophiopogonanone A, 6-aldehydo-isoophiopogonanone B, methylophiopogonanone A and methylophiopogonanone B from fibrous roots of *Ophiopogon japonicus* [11]. The diverse type flavonoids were synthesized in plant species via shikimate and phenylpropanoid pathway. Several types enzyme as DAHP synthase, DHQ synthase, SA kinase, PAT, ADT, 4CL, CHS, CHI, F3H, DFR

Shikimate pathway plays high potential role in the biosynthesis of flavonoids. Several key enzymes are involved in this pathway for biosynthesis of shikimic acid. This pathway starts with the aldol condensation reaction of phosphoenol pyruvate (PEP) and D-erythrose 4-phosphate (E4P) to generate seven carbon keto acid, 3-deoxy-D-arabino-heptulosonate −7-phosphate (DAHP). This reaction catalyzes by 3-deoxy-D-arabino-heptulosonate −7-phosphate synthase (DAHPS) enzyme. The DAHPS is a highly potential enzyme of the shikimate pathway. Two DAHPS genes as DHS1 and DHS2 are found in *Arabidopsis thaliana* plants [14]. From literature, it is identified that DHS1 is more produced by infiltration or by physical wounding with pathogen in both tomato and Arabidopsis [15]. The DAHP is transformed to 3-dehydroquinic acid (DHQ ) by intramolecular cyclization reaction

In most bacteria, DHQS is monofunctional and in some organism, it behaves multifunctional enzyme, which catalyze 2, 3, 4, and 5 steps of the shikimate pathway. The DHQS is a small part of larger AROM protein, which is pentafunctional peptide containing enzyme [16, 17]. The *Neurospora crassa* and *Aspergillus nidulans* DHQS enzyme found in nature as part of the AROM protein [18]. The DHQ con-

In the fourth step, DHS is transformed into shikimic acid by removing water

The EPSPS is activating of shikimic acid 3-phosphate in the sixth step reaction of the shikimate pathway. According to intrinsic glyphosate sensitivity, it enzyme has been classified as a class I EPSP synthases and class II EPSP synthases [21, 22].

molecule. The phosphorylation of shikimic acid is done by activating of shikimate kinase enzyme in the fifth step reaction. The shikimic acid with ATP is phosphorylated at the 5-OH group of shikimic acid converts into shikimic acid 3-phosphate (S3P). The shikimate kinase enzyme is not found in the human cell, but is an essential enzyme of many bacterial pathogens [19, 20]. The shikimic acid 3-phosphate converts into 3-enolpyruvyl shikimate −5-P (EPSP) by EPSP synthase

verts into 3-dehydroshikimic acid (DHS) by losing a water molecule.

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enzymes.

within one of two functional groups as fungal type bifunctional CS and plant, bacterial type monofunctional CS [24, 25].

The chorismate mutase (CM) is a first step enzyme of the tyrosine and phenylalanine biosynthesis. It activates of chorismic acid, which converts into prephenic acid by claisen rearrangement [26]. On the basis functional and structural, multiple form of this enzyme exists. Some monofunctional example from *Serratia rubidaea*, *Bacillus subtilis* [27], *Aspergillus nidulans* [28]. In presence of this enzyme, chorismic acid change into prephenic acid.

The prephenate aminotransferase (PAT) play a key role in phenylalanine biosynthesis. It catalyzes first step product (prephenic acid) into arogenic acid [29]. The arogenate dehydratase (ADT) is a last step enzyme of phenylalanine biosynthesis, which catalyzes of arogenic acid into amino acid phenylalanine [30]. In the arabidopsis genome, six ADT genes as ADT1-ADT6 are found, whereas ADT4 and ADT5 were dominant in roots and stems [31]. The shikimate pathway with enzyme activity is summarized in **Figure 2**.
