Phenylpropanoids shikimate pathway

Precursors of phenylpropanoids are synthesized from two basic pathways the shikimic acid pathway and the malonic pathway (see Fig. 3.1). The shikimic acid pathway produces most plant phenolics, whereas the malonic pathway, which is an important source of phenolics in fungi and bacteria, is less significant in higher plants. The shikimate pathway converts simple carbohydrate precursors into the amino acids phenylalanine and tyrosine. The synthesis of an intermediate in this pathway, shikimic acid, is blocked by the broad-spectrum herbicide glyphosate (i.e., Roundup). Because animals do not possess this synthetic pathway, they have no way to synthesize the three aromatic amino acids (i.e., phenylalanine, tyrosine, and tryptophan), which are therefore essential nutrients in animal diets. 

Ring B and the central three-carbon bridge forming the C ring (see Fig. 5.1) originate from the amino acid phenylalanine, itself a product of the shikimate pathway, a plastid-based process which generates aromatic amino acids from simple carbohydrate building blocks. Phenylalanine, and to a lesser extent tyrosine, are then fed into flavonoid biosynthesis via phenylpropanoid (C6-C3) metabolism (see Fig. 5.1). 

To what extent is the response of cytosolic and plastidic isozymes of the shikimate pathway coordinated or coupled with one another and to alterations in expression of enzymes of the flavonoid and phenylpropanoid-pathway segments Some of the emerging information is given in Figure 6. Thus, light induction, well known to induce PAL and enzymes of the flavonoid pathway, also induces both DS-Mn and DS-Co in parsley cell cultures (49). However, only the cytosolic CM-2 (and not the plastidic CM-1) was induced. Fungal elicitor was reported to induce only DS-Mn—not DS-Co or either of the chorismate mutase isozymes (49). Previous studies... 

The observations that flavonols are not involved in the fertilization process in certain species, and that this function can be completed using other compounds, suggest that flavonols only affect fertility indirectly. There are various examples of cross-talk between branch pathways of phenylpropanoid metabolism, or the shikimate pathway. The absence of flavonols in maize and Petunia could affect the accumulation of other compounds that are more specifically required for male fertility. Thus, differences between species in terms of flavonoid... 

The general phenylpropanoid pathway links the shikimate pathway to the lignin branch pathway. The latter pathway leads to the formation of a series of hydroxycinnamic acids and hydroxycinnamoyl-CoA esters varying in their degrees of hydroxylation and methylation [5]. 

The general phenylpropanoid pathway begins with the deamination of L-phenylalanine to cinnamic acid catalyzed by phenylalanine ammonia lyase (PAL), Fig. (1), the branch-point enzyme between primary (shikimate pathway) and secondary (phenylpropanoid) metabolism [5-7]. Due to the position of PAL at the entry point of phenylpropanoid metabolism, this enzyme has the potential to play a regulatory role in phenolic-compound production. The importance of this is illustrated by the high degree of regulation both during development as well as in response to environmental stimuli. 

THE SHIKIMATE PATHWAY AROMATIC AMINO ACIDS AND PHENYLPROPANOIDS... 

It has been noted that the chemical diversity of plant phenolics is as vast as the plant diversity itself. Most plant phenolics are derived directly from the shikimic acid (simple benzoic acids), shikimate (phenylpropanoid) pathway, or a combination of shikimate and acetate (phenylpropanoid-acetate) pathways. Products of each of these pathways undergo additional structural elaborations that result in a vast array of plant phenolics such as simple benzoic acid and ciimamic acid derivatives, monolig-nols, lignans and lignin, phenylpropenes, coumarins, stilbenes, flavonoids, anthocyanidins, and isollavonoids. 

The lignans are secondary plant metabolites biosynthetically derived from the shikimate pathway. They possess diverse structures, usually dimers of phenylpropanoid units, although compounds containing three, four or even five such units, have been reported. The number of higher oligomers identified is currently increasing. 

Phenolic compounds include a wide range of secondary metabolites that are biosynthesised from carbohydrates through the shikimate pathway [14]. This is the biosynthetic route to the aromatic amino acids, phenylalanine, tyrosine, and tryptophan, and only occurs in microorganisms and plants. In the first step, the glycolytic intermediate phosphoenol pyruvate and the pentose phosphate intermediate erythrose-4-phosphate are condensed to 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP), a step catalysed by DAHP synthase. Intermediates of the shikimate pathway are 3-dehydroquinate, shikimate, and chorismate (Fig. 1). Phenylalanine is biosynthesised from chorismate, and from phenylalanine all the phenylpropanoids. Quinate is produced from 3-dehydroquinate and incorporated into chlorogenic and isochlorogenic acids (caffeoyl quinic acids) by combination with caffeic acid. Gallic acid is produced from shikimate. 

All phenylpropanoids are derived from cinnamic acid, which is formed from phenylalanine through the action of phenylalanine ammonia-lyase (PAL), which is considered the branch point enzyme between primary (shikimate pathway) and secondary metabolism [15]. 

The biosynthetic pathway (Figure 10.5) of polyphenols, including phenolic acids is well known. Phenylalanine formed in plants via the shikimate pathway is a common precursor for most of the phenolic compounds. Forming hydroxycinnamic acids from phenylalanine requires hydroxylation and methylation steps. The formation of hydroxybenzoic acids is simple and they can directly be formed from the corresponding hydroxycinnamic acids with the loss of acetate or with an alternate path stemming from an intermediate in the phenylpropanoid pathway [69,77,78]. 

EPSPS is the sixth enzyme in the shikimate pathway that leads to the biosynthesis of aromatic amino acids, tryptophan, tyrosine, and phenylalanine. These aromatic amino adds along with intermediates of the pathway give rise to important secondary metabolites commonly referred to as phenylpropanoids that include phenolics, lignins, tannins, phytoalexins, etc. [1]. The shikimate pathway is localized in plastids and EPSPS is a key enzyme in regulating the flux through the pathway. 

Benzoic and cinnamic acid derivatives and flavonoids are the two most distributed phenolics within plants. Polyphenolic units are biosynthesized via shikimate pathway, resulting in cinnamic acids C -C phenylpropanoid building block that also contributes to other plant phenolics backbones such as those from flavonoids (Q-Ca-Ce), anthocyanidins (C6-C3-C6), and coumarins (C6-C3). Stilbeneoids (C6-C2-C6) and benzoic acid derivatives (Cfi-Ci) such as gallic and ellagic acids are also synthesized through this metabolic pathway (Fig. 1). 

The precursor substrates and enzymes necessary for the first committed steps often appear to have been recruited from primary metabolic pathways, such as glycolysis, the Krebs cycle, the pentose phosphate pathway and the shikimate pathway [32], For example, the aromatic amino acid s L-phenylalanine and L-tyrosine, produced by the shikimate pathway, are precursors for a wide spectrum of natural products including phenylpropanoids, flavonoids, lignins, coumarins, cyanogenic glycosides, glucosinolates, and alkaloids [33],... 

This complexity of EOs phytochemistry led to a certain inconsistency of the chemical composition of an essential oil. In fact, several factors influence the balance of the compounds within EOs. Terpenoids and isoprenoid are synthesized through secondary metabolism of the plant. Monoterpenes are biosynthesized in plastid via two 5-carbon precursors, that is, isopentenyl pyrophosphate and dimethylallyl pyrophosphate, which condense to give the monoterpenes (10-carbon). The sesquiterpenes (15-carbon) are formed via the mevalonate pathway in the cytosol. Phenylpropanoids are derived mainly from the shikimate pathway [5]. 

Natural Products Derived from the Shikimate Pathway and Phenylpropanoids... 

The Shikimate Pathway in Higher Plants Phenylpropanoid Compounds and their Derivatives... 

Figure 5.15, The Shikimate pathway in higher plants phenylpropanoid compounds and their derivatives summary...

An alternate fate of the products of photosynthesis that are channeled through the shikimate pathway is for 3-dehydroshikitnic acid to be directed to L-phenylalanine and so enter the phenylpropanoid pathway (Figure 1.15). Phenylalanine ammonia-lyase catalyses the first step in this pathway, the conversion of L-phenylalanine to cinnamic acid, which in a reaction catalysed by cinnamate 4-hydroxylase is converted to p-coumaric acid which in turn is metabolized to p-coumaroyl-CoA by p-coumarate CoA ligase. Cinnamic add is... 

The earliest references to cinnamic acid, cinnamaldehyde, and cinnamyl alcohol are associated with thek isolation and identification as odor-producing constituents in a variety of botanical extracts. It is now generally accepted that the aromatic amino acid L-phenylalanine [63-91-2] a primary end product of the Shikimic Acid Pathway, is the precursor for the biosynthesis of these phenylpropanoids in higher plants (1,2). 

Plant metabolism can be separated into primary pathways that are found in all cells and deal with manipulating a uniform group of basic compounds, and secondary pathways that occur in specialized cells and produce a wide variety of unique compounds. The primary pathways deal with the metabolism of carbohydrates, lipids, proteins, and nucleic acids and act through the many-step reactions of glycolysis, the tricarboxylic acid cycle, the pentose phosphate shunt, and lipid, protein, and nucleic acid biosynthesis. In contrast, the secondary metabolites (e.g., terpenes, alkaloids, phenylpropanoids, lignin, flavonoids, coumarins, and related compounds) are produced by the shikimic, malonic, and mevalonic acid pathways, and the methylerythritol phosphate pathway (Fig. 3.1). This chapter concentrates on the synthesis and metabolism of phenolic compounds and on how the activities of these pathways and the compounds produced affect product quality. 

Phenylalanine Ammonia-Lyase. The building units of lignin are formed from carbohydrate via the shikimic acid pathway to give aromatic amino acids. Once the aromatic amino acids are formed, a key enzyme for the control of lignin precursor synthesis is phenylalanine ammonia-lyase (PAL) (1). This enzyme catalyzes the production of cinnamic acid from phenylalanine. It is very active in those tissues of the plant that become lignified and it is also a central enzyme for the production of other phenylpropanoid-derived compounds such as flavonoids and coumarins, which can occur in many parts of the plant and in many different organs (35). Radioactive phenylalanine and cinnamic acid are directly incorporated into lignin in vascular tissue (36). 

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