**3. Phenylpropanoid pathway**

The shikimate pathway plays the main role in the biosynthesis of flavonoids, which provides amino acid phenylalanine. The phenylalanine ammonia lyase (PAL) is an enzyme of first step reaction in phenylpropanoid pathway. The presence of this

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

enzyme has been reported in different types of plant species [32] as certain fungi [33], few prokaryotic organisms, including *Streptomyces* [34, 35], algae, including *Dunaliella marina* [36] and detected in several species representing gymnosperms, ferns, lycopods, monocots, and dicots [37]. This enzyme converts phenylalanine

The cinnamate −4-hydroxylase (C4H) plays a crucial role in conversion of trans-cinnamic acid in 4-coumaric acid. This acid, yielding 4-coumaroyl-CoA by catalyzing of 4-coumaroyl-CoA-ligase (4CL). The 4-coumaroyl-CoA-ligase (4CL) plays a pivotal role in phenylpropanoid biosynthesis pathway and produced coumarin skeleton. Mostly, a multiple isoform of 4CL are found in higher plants. These isoforms have distinct catalytic properties and expression profiles in plant

The initial step of flavonoids biosynthesis is the condensation reaction of one molecule 4-coumaroyl-CoA with three molecules of malonyl-CoA to yielding chalcone (2′,4′,6′,4-tetrahydroxy chalcone) by catalyzing the chalcone synthase (CHS) enzyme [39]. chalcone synthase (CHS) enzyme plays key role in the biosynthesis of flavonoids and isoflavonoids. The plant polyketide synthase is a big family called superfamily, CHS is a member of this family [40]. The chalcone isomerized into flavanone by activating of chalcone flavanone isomerase (CHI) enzyme. The flavanone is the intermediate pathway of flavonoids, which divided into many different flavonoids classes [41, 42]. The modification of flavanone into the basic skeleton of flavonoids, depends on the species and a group of enzymes as hydroxylases, reductases, isomerases [43]. The phenylpropanoid pathway in the biosynthesis of

The shikimate and phenylpropanoid pathway play important role in biosynthesis of flavonoids. After this pathway flavonoids pathway starts, which produce various diverse type flavonoids in presence of several enzymes. The isoflavonoid synthase (IFS) is a main enzyme, which converts a flavanone into isoflavone. In soybean, two isoform of IFS genes as IFS-1 and IFS-2 are found, which play a crucial role in the isoflavones biosynthesis [44, 45]. The role of this enzyme summarized in

The flavonol synthase (F3H) is a key enzyme of the biosynthesis in the central flavonoid pathway. It plays a pivotal role in the conversion of flavanone into dihydroflavonol. It has been isolated from various plant species (more than 50 plants) [46, 47]. The flavonol synthase (FLS) is a highly activating enzyme, which converts of dihydroflavonol into flavonol. The first FLS gene was known from *P. hybrida* [48] and other FLS gene were known from various plant species as *A. thaliana* [49],

The dihydroflavonol reductase (DFR) is a essential enzyme, which catalyzes dihydroflavonol into leucoanthocyanidin and are precursors of anthocyanidins and proanthocyanidins [51]. The DFR genes have been cloned in several plant species as *Lotus japonicas* [52], *Ginkgo biloba* [53], *Brassica rapa* [54]. *The DFR can overexpres-*

*The proanthocyanidins is known condensed tannins (polymers), which produced by condensation of flavan-3-ol monomeric units as epicatechin and catechin. It catalyzes in the presence of two enzymes as* leucoanthocyanidin reductase (LAR) and anthocyanidin reductase (ANR). The LAR is the main enzyme of anthocyanin biosynthesis pathway, which converts leucoanthocyanidin into catechin, while ANR converts anthocyanidin into epicatechin [57–59]. *The CsLAR gene is found in tobacco, which* 

*sion in apple and tobacco, which increase anthocyanin production* [55, 56].

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

flavonoids summarized in **Figure 3**.

**4. Flavonoids pathway**

*E. grandiflorum* [50] etc.

**Figure 4**.

tissue [38].

into cinnamic acid and remove the ammonium ion.

**Figure 3.** *Phenylpropanoid pathway in biosynthesis of flavonoids.*

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

enzyme has been reported in different types of plant species [32] as certain fungi [33], few prokaryotic organisms, including *Streptomyces* [34, 35], algae, including *Dunaliella marina* [36] and detected in several species representing gymnosperms, ferns, lycopods, monocots, and dicots [37]. This enzyme converts phenylalanine into cinnamic acid and remove the ammonium ion.

The cinnamate −4-hydroxylase (C4H) plays a crucial role in conversion of trans-cinnamic acid in 4-coumaric acid. This acid, yielding 4-coumaroyl-CoA by catalyzing of 4-coumaroyl-CoA-ligase (4CL). The 4-coumaroyl-CoA-ligase (4CL) plays a pivotal role in phenylpropanoid biosynthesis pathway and produced coumarin skeleton. Mostly, a multiple isoform of 4CL are found in higher plants. These isoforms have distinct catalytic properties and expression profiles in plant tissue [38].

The initial step of flavonoids biosynthesis is the condensation reaction of one molecule 4-coumaroyl-CoA with three molecules of malonyl-CoA to yielding chalcone (2′,4′,6′,4-tetrahydroxy chalcone) by catalyzing the chalcone synthase (CHS) enzyme [39]. chalcone synthase (CHS) enzyme plays key role in the biosynthesis of flavonoids and isoflavonoids. The plant polyketide synthase is a big family called superfamily, CHS is a member of this family [40]. The chalcone isomerized into flavanone by activating of chalcone flavanone isomerase (CHI) enzyme. The flavanone is the intermediate pathway of flavonoids, which divided into many different flavonoids classes [41, 42]. The modification of flavanone into the basic skeleton of flavonoids, depends on the species and a group of enzymes as hydroxylases, reductases, isomerases [43]. The phenylpropanoid pathway in the biosynthesis of flavonoids summarized in **Figure 3**.

#### **4. Flavonoids pathway**

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

bacterial type monofunctional CS [24, 25].

acid change into prephenic acid.

activity is summarized in **Figure 2**.

**3. Phenylpropanoid pathway**

within one of two functional groups as fungal type bifunctional CS and plant,

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

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

The shikimate pathway plays the main role in the biosynthesis of flavonoids, which provides amino acid phenylalanine. The phenylalanine ammonia lyase (PAL) is an enzyme of first step reaction in phenylpropanoid pathway. The presence of this

**90**

**Figure 3.**

*Phenylpropanoid pathway in biosynthesis of flavonoids.*

The shikimate and phenylpropanoid pathway play important role in biosynthesis of flavonoids. After this pathway flavonoids pathway starts, which produce various diverse type flavonoids in presence of several enzymes. The isoflavonoid synthase (IFS) is a main enzyme, which converts a flavanone into isoflavone. In soybean, two isoform of IFS genes as IFS-1 and IFS-2 are found, which play a crucial role in the isoflavones biosynthesis [44, 45]. The role of this enzyme summarized in **Figure 4**.

The flavonol synthase (F3H) is a key enzyme of the biosynthesis in the central flavonoid pathway. It plays a pivotal role in the conversion of flavanone into dihydroflavonol. It has been isolated from various plant species (more than 50 plants) [46, 47]. The flavonol synthase (FLS) is a highly activating enzyme, which converts of dihydroflavonol into flavonol. The first FLS gene was known from *P. hybrida* [48] and other FLS gene were known from various plant species as *A. thaliana* [49], *E. grandiflorum* [50] etc.

The dihydroflavonol reductase (DFR) is a essential enzyme, which catalyzes dihydroflavonol into leucoanthocyanidin and are precursors of anthocyanidins and proanthocyanidins [51]. The DFR genes have been cloned in several plant species as *Lotus japonicas* [52], *Ginkgo biloba* [53], *Brassica rapa* [54]. *The DFR can overexpression in apple and tobacco, which increase anthocyanin production* [55, 56].

*The proanthocyanidins is known condensed tannins (polymers), which produced by condensation of flavan-3-ol monomeric units as epicatechin and catechin. It catalyzes in the presence of two enzymes as* leucoanthocyanidin reductase (LAR) and anthocyanidin reductase (ANR). The LAR is the main enzyme of anthocyanin biosynthesis pathway, which converts leucoanthocyanidin into catechin, while ANR converts anthocyanidin into epicatechin [57–59]. *The CsLAR gene is found in tobacco, which* 

**Figure 4.** *The essential role of enzyme in flavonoids pathway.*

*accumulation of higher level of epicatechin than catechin while ANR in tea and grapevine is involved in biosynthesis of mixture of catechin and epicatechin from anthocyanidin* [60, 61]. *The proanthocyanidins have been reported from various plant species* [62, 63]. *The catalyzing properties of these enzymes are showed in Figure 5.*

#### **4.1 Chalcones**

Chalcone synthase plays potential role in the biosynthesis of flavonoids/ isoflavonoids pathway. The CHS is a member of the polyketide synthase family, which play a key role flowering plant as providing floral pigment, insect repellents, UV Protectants and antibiotics [64]. The chalcones are called open chain

**93**

**Figure 7.**

**Figure 6.**

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

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

*Various types chalcones isolated from several plants.*

*Diverse type of flavan and flavan-3-ol reported from parts of plants.*

**Figure 5.** *Biosynthesis of tannins and anthocyanin in flavonoids pathway.*

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

**Figure 6.**

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

*accumulation of higher level of epicatechin than catechin while ANR in tea and grapevine is involved in biosynthesis of mixture of catechin and epicatechin from anthocyanidin* [60, 61]. *The proanthocyanidins have been reported from various plant species* [62, 63].

Chalcone synthase plays potential role in the biosynthesis of flavonoids/ isoflavonoids pathway. The CHS is a member of the polyketide synthase family, which play a key role flowering plant as providing floral pigment, insect repellents, UV Protectants and antibiotics [64]. The chalcones are called open chain

*The catalyzing properties of these enzymes are showed in Figure 5.*

*The essential role of enzyme in flavonoids pathway.*

**92**

**Figure 5.**

*Biosynthesis of tannins and anthocyanin in flavonoids pathway.*

**4.1 Chalcones**

**Figure 4.**

*Various types chalcones isolated from several plants.*

**Figure 7.** *Diverse type of flavan and flavan-3-ol reported from parts of plants.*

flavonoids, which have 15 carbon structure and arranged in C6-C3-C6 skeleton. The modification of chalcones can be done by methylation, condensation, and hydroxylation. These chalcones can be distributed in many parts of plants as fruits, seed, bark, stem, flowers [65].

Various diverse type chalcones have been reported from many plant species such as 2,4-dihydroxy-30-methoxy-40-ethoxychalcone from *Caragana pruinosa* [66], two chalcones, sappanchalcone and 3-deoxysappanchalcone from *Haematoxylum campechianum* [67], 4,2′,4′-trihydroxy-chalcone 4,2′-dihydroxy-4′- methoxychalcone, 4-hydroxylonchocarpin, crotmadine chalcones *Codonopsis cordifolioidea* root [68], and crotaramin chalcone from *Crotalaria ramosissima* plant [69]. These chalcones are showed in **Figure 6**.

## **4.2 Flavan and Flavan-3-ol**

Many different flavan and flavan-3-ol are summarized in **Figure 7**, which have been isolated from many plants as afzelechin from steam bark of *Pinus halepensis* [70], oncoglabrinol C from *Oncocalyx glabratus* [71], epicatechin, and 3,5,7,4′-tetrahydroxy flavan from stem bark of *Embelia schimperi* [72], three flavan-3-ol derivatives as (+)-afzelechin, (+)-afzelechin-7-O-α-Larabinofuranoside and (+)-afzelechin-7-O-β-D-apiofuranoside from *Polypodium vulgare* L. rhizomes [73].

**95**

**Figure 9.**

*Diverse structure of isoflavonoids from plants species.*

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

Many different structures of flavones and flavanone are synthesized via shikimate and flavonoids pathway. These structures of these are showed in **Figure 8**. Several type of flavones and flavanone were isolated such as apigenin 7-O-β-D-glucopyranoside, dimethylchrysin, trimethylapigenin, 5,7,3′,4′-tetrahydroxyflavone (Luteolin) from *Sterculia foetida* leaves [74], three new flavan-flavanones as friesodielsones A, friesodielsones B, friesodielsones, from *Friesodielsia desmoides* leaves [75], and flavonoids (flavones) as apigenin-7,4′-dimethylether, genkwanin from *Aquilaria sinensis*

The diverse type structure of isoflavonoids was synthesized from flavanone, which have been reported several plants as corylifol A, neobavaisoflavone, and irisflorentin from *Cytisus striatus* [77], formoninetin and biochanin A from *Hylastinus obscurus* [78]. One new leptoisoflavone A (a rare 5-membered dihydrofuran ring) from *Limonium leptophyllum* [79], 2,2′-trimethoxy-6,8-dihydroxy-isoflavone from the ethanol extract of *Thespesia populnea* bark [80] and isoflavones, genistein and

Several type of flavonol were reported from parts of plants as myricetin 3-O-(2″,4″-di-O-acetyl)-α-L-rhamnopyranoside from *Myrsine Africana* [82], flavonoid glycoside named as 3'-*O*-methyl quercetin-3-glucose-6-gallic acid from *Cordia oblique* leaves [83], 2-(3, 4-dihydroxyphenyl)-3, 5, 7-trihydroxy-4H-chromen-4-one

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

daidzein from *Hericium erinaceum* (**Figure 9**) [81].

**4.3 Flavone-flavanone**

leaves [76].

**4.5 Flavonol**

**4.4 Isoflavonoids**

**Figure 8.** *Structural diversity of flavones and flavanone.*

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

#### **4.3 Flavone-flavanone**

*Bioactive Compounds - Biosynthesis, Characterization and Applications*

fruits, seed, bark, stem, flowers [65].

chalcones are showed in **Figure 6**.

**4.2 Flavan and Flavan-3-ol**

*vulgare* L. rhizomes [73].

flavonoids, which have 15 carbon structure and arranged in C6-C3-C6 skeleton. The modification of chalcones can be done by methylation, condensation, and hydroxylation. These chalcones can be distributed in many parts of plants as

Various diverse type chalcones have been reported from many plant species such as 2,4-dihydroxy-30-methoxy-40-ethoxychalcone from *Caragana pruinosa* [66], two chalcones, sappanchalcone and 3-deoxysappanchalcone from *Haematoxylum campechianum* [67], 4,2′,4′-trihydroxy-chalcone 4,2′-dihydroxy-4′- methoxychalcone, 4-hydroxylonchocarpin, crotmadine chalcones *Codonopsis cordifolioidea* root [68], and crotaramin chalcone from *Crotalaria ramosissima* plant [69]. These

Many different flavan and flavan-3-ol are summarized in **Figure 7**, which have been isolated from many plants as afzelechin from steam bark of *Pinus halepensis* [70], oncoglabrinol C from *Oncocalyx glabratus* [71], epicatechin, and 3,5,7,4′-tetrahydroxy flavan from stem bark of *Embelia schimperi* [72], three flavan-3-ol derivatives as (+)-afzelechin, (+)-afzelechin-7-O-α-L-

arabinofuranoside and (+)-afzelechin-7-O-β-D-apiofuranoside from *Polypodium* 

**94**

**Figure 8.**

*Structural diversity of flavones and flavanone.*

Many different structures of flavones and flavanone are synthesized via shikimate and flavonoids pathway. These structures of these are showed in **Figure 8**. Several type of flavones and flavanone were isolated such as apigenin 7-O-β-D-glucopyranoside, dimethylchrysin, trimethylapigenin, 5,7,3′,4′-tetrahydroxyflavone (Luteolin) from *Sterculia foetida* leaves [74], three new flavan-flavanones as friesodielsones A, friesodielsones B, friesodielsones, from *Friesodielsia desmoides* leaves [75], and flavonoids (flavones) as apigenin-7,4′-dimethylether, genkwanin from *Aquilaria sinensis* leaves [76].
