Chorismic acid compounds derived from

The naturally occurring naphthoquinones such as lawsone and juglone are products of the shikimic acid pathway to aromatic amino-acids but the path which leads to these naphthoquinones branches from the main pathway before the formation of aromatic compounds, probably no later than chorismic acid.It will be most interesting to see whether the biosynthesis of shihunine also follows this route all the other bases of plant origin which arise from products of the shikimic acid pathway derive from aromatic precursors. 

The biosynthesis of compounds derived from shikimic acid is closely linked to that of isomers of vitamin K (35) (Fig. 6.7). In plants and in microorganisms, die aromatic ring is formed via the shikimate pathway, which does not exist in animals. Only recently has it been established that vitamin K synthesis branches from wo-chorismic acid (36) and not from chorismic acid (37). fro-Chorismic acid (36) is derived from shikimic acid (see Chapter 7) (Leistner, 1986). Both of the cyclization steps leading to naphthoquinones and vitamin K are unusual in plants. 

Use of Mutants in Biosynthetic Studies Formation of Chorismic Acid Derivatives of Chorismic Acid Biosynthesis of Tryptophan Indole 3-Acetic Acid Avenalumins from Oats DIMBOA and Related Compounds Biosynthesis of Phenylalanine and Tyrosine Compounds Derived from Shikimic Pathway Intermediates... 

In some fungi, salicylic acid (65) and related compounds, such as 6-methylsalicylic acid, are derived from acetate-ma-lonate pathways. In bacterial systems, similar compounds are derived from chorismic acid via isochorismic acid see Chapter 7). Salicylic acid often is found in species of Salix... 

Phylloquinone and menaquinone are derived from chorismic acid, which results from 3-phosphoenolpyruvic acid (a product of glycolysis) and D-erythrose 4-phosphate (a product of the pentose and Calvin cycles) as a starting compound for the biosynthesis of phenylalanine, tyrosine and tryptophan. It is transformed into iso-chorismic acid other carbon atoms are derived from 2-oxoglutaric acid. The side chain is provided by ph)4yl diphosphate or by polyprenyl diphosphates, which are formed from geranylgeranyl diphosphate. The final reaction is a methylation at C-2. 

Microbes and plants synthesize aromatic compounds to meet their needs of aromatic amino acids (L-Phe, L-Tyr and L-Trp) and vitamins. The biosynthesis of these aromatics [69] starts with the aldol reaction of D-erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP), which are both derived from glucose via the central metabolism, into DAHP (see Fig. 8.13). DAHP is subsequently converted, via a number of enzymatic steps, into shikimate (SA) and eventually into chorismate (CHA, see later), which is the common intermediate in the biosynthesis of the aromatic amino acids [70] and vitamins. 

The reaction in the shikimic acid pathway is, of course, the [3,3]-sigmatropic shift in which chorismic acid rearranges to prephenic acid on the way to aromatic rings (p. 1403). The simpler reaction given here is one of the family of reactions from Chapter 36 (pp. 944-6) using an allylic alcohol and an enol derivative of a carbonyl compound. In this case we have the enol ether of a ketone. We must combine these to make an allyl vinyl ether for rearrangement. 

The benzene ring of the aromatic amino acids is formed by the shikimate pathway. The carbons in the benzene ring are derived from erythrose-4-phosphate and phosphoenolpyruvate. These two molecules condense to form 2-keto-3-deoxy-arabinoheptulosonate-7-phosphate, a molecule that is subsequently converted to chorismate in a series of reactions that are outlined in Figure 14.10. Choris-mate is the branch point in the syntheses of various aromatic compounds. 

Figure 21.12 provides an overview of the biosynthesis of aromatic amino acids and histidine. All of the carbons in phenylalanine and tyrosine are derived from erythrose-4-phosphate and phosphoenolpyruvate. A key intermediate in synthesis of virtually all aromatic compounds (including p-aminobenzoic acid) in plant and bacterial cells is shikimic acid. Shikimic acid gives rise to chorismate... 

The biosynthesis of these anthraquinones parallels those of the menoquinones in bacteria and naphtoquinones of plants for example juglone, vitamin K and lawsone. These compounds are also derived from shikimic (or chorismic) and a-ketoglutaric acids via o-succinylbenzoic acid [5,24]. 1,4-Dihydroxy-2-naphtoic acid is the branching point in the biosynthesis of menoquinones, naphtoquinones and anthraquinones [4],... 

The three aromatic amino acids that are biosynthesized in the shikimic acid pathway have much in common. The many stereochemical events occurring between the condensation of compounds 288a and 289 derived from carbohydrates to the formation of prephenic acid 296 have been extensively reviewed including a recent review by ourselves (82), and so we have summarized the stereochemistry of the biosynthesis in Scheme 79. Prephenic acid 296 leads to phenylalanine 297 and tyrosine 298. The mem-substituted amino acids 299 are derived from chorismate 295, as is tryptophan 302, as shown. 

Biosynthesis Like other aromatic amino acids, e.g., Phe and Tyr, Trp is formed on the shikimic acid pathway. There is a branching point at chorismic acid one branch leads to Phe and Tyr, the other to Trp choris-mic acid - anthranilic acid (anthranilic acid synthase, EC 4.1.3.27)- A-(5 -0-phosphoribosyl)-anthranilic acid (anthranilic acid phosphoribosyl transferase, EC 2.4.2.18)- 1 -o-carboxyphenylamino-1 -deoxyribu-lose 5-phosphate [A-(5 -phosphoribosyl)anthranilic acid isomerase]- indole-3-glycerol phosphate (in-dole-3-glycerol phosphate synthase, EC 4.1.1.48) - indole (tryptophan synthase, EC 4.2.1,20)+serine - Trp. Many biologically active indole compounds are derived from Trp, e. g., 5-hydroxytryptophan, 5-hydroxy-tryptamine ( serotonin), and melatonin as well as many indole alkaloids. 

Tryptophan is an essential amino acid for most organisms. In plants and bacteria, this compound is derived from chorismic acid. Many groups of secondary compounds are formed from tryptophan among these are several simple amine derivatives and a number of alkaloids. 

The first step in the formation of tryptophan involves conversion of chorismate (9) to anthranilate (11) (Fig. 7.4). Although the reaction is not well understood, it is catalyzed by the enzyme anthranilate synthase and utilizes L-gluta-mine. By means of specifically labeled chorismic acid, it was determined that the protonation involved in the formation of anthranilic acid had occurred from the re face (Figure 4) (Floss, 1986). Anthranilic acid (11) also serves as an intermediate for the synthesis of a number of secondary compounds and occurs free and as various derivatives in many plants and other organisms (Dewick, 1989). 

Another series of compounds that appear to be derived from ijo-chorismic acid are cyclohexene oxides such as cro-tepoxide (36), senepoxide (37), and pipoxide (38) from Croton macrostachys (Euphorbiacee), Uvaria zeylanica (An-nonaceae), and Piper hookeri (Piperaceae), respectively (Fig. 7.13). These compounds have demonstrated antitumor activity (Jolad et al., 1981). 

Dehydroquinic acid, shikimic acid, and chorismic acid are carboxylated compounds containing a six-membered carbocyclic ring with one or two double bonds (Fig. 143). The secondary products derived from these substances either still contain the ring and the C -side chain of the acids (see the structure of the benzoic acid derivatives, of anthranilic and 3-hydroxyanthranilic esters, D 8, D 8.2, D 8.4 and D 8.4.1) or have additional rings (see the formulae of naphthoquinones and anthraquinones, D 8.1, of quinoline, acridine, and benzodiazepine alkaloids, D 8.3.2). The carbon skeletons may be substituted by isoprenoid side chains (see the structure of ubiquinones, D 8.3) and may carry different functional groups, e.g., hydroxy, carboxy, methoxy, and amino groups. 

Dehydroquinic, shikimic, and chorismic acids as well as the secondary products derived from these compounds are built in microorganisms and plants. 

Fig. 143. Formation of dehydroquinic, dehydroshikimic, shikimic and chorismic acids and secondary products derived from these compounds...

The naphthoquinone nucleus of the above-mentioned compounds originates from chorismic acid and y-hydroxybutyryl-2 -thiamine pyrophosphate ( activated succinylsemialdehyde ) derived from oc-ketoglutarate (C 4). An important intermediate is 2-succinylbenzoic acid. Naphthohydroquinone-2-carboxylic acid is the first naphthalene derivative formed. Juglone is synthesized via a symmetrical intermediate, in contrast to the vitamins K, e.g., phylloquinone, and to lawsone. The side chain of phylloquinone derives from phytol (D 6.3). 

Research in David Sprinson s laboratory at Columbia University, in part contemporary with the research outlined in the preceding pages, has unraveled the earliest stages of the sequence and the derivation of the first, non-cyclic intermediate, DAMP. In the same laboratory, Judith Levin discovered 5-enolpyruvylshikimate 3-phosphate and predicted the existence and correct structure of the next, and last one, of the common intermediates, the compound from which the pathways to the individual primary aromatic products branch off. Isolation and structure proof of this branchpoint intermediate, chorismic acid, by the Australian workers F. Gibson, L.M. Jackman, and J.M. Edwards completed the elucidation of the general pathway. 

Until recently it was believed that chorismic acid is the branch point compound that links the shikimate pathway to the vitamin K biosynthetic pathway. "" Recent results show that this is not true (vide infra). Since vitamin K was assumed to be derived from chorismic acid, it was concluded that plant quinones which, like vitamin K, are synthesized in plants via the shikimate pathway are also derived from chorismic acid. Since chorismic acid is not the immediate precursor of the benzene ring of vitamin K, it probably is also not the immediate precursor of plant quinones such as alizarin, lucidin, or juglone. ... 

Basically, the shikimic acid pathway involves initial condensation of phosphoenolpyruvate (PEP) from the glycolysis process with erythrose-4-phosphate derived from the oxidative pentose phosphate cycle. A series of reactions leads to shikimic acid, which is then phosphorylated. The phosphorylated shikimic acid combines with a second molecule of PEP to yield prephenic acid via chorismic acid intermediate. Prephenic acid is then decarboxylated to form phenyl-pyruvate or p-hydroxyphenylpyruvate. On transamination, these two compounds yield phenylalanine and tyrosine, respectively. 

The shikimate pathway provides the precursors for benzoic acid derivatives and phenylpropa-noid compounds in plants (Fig. 15). Shikimate is biosynthesized from D-erythrose-4-phosphate and phosphoenolpyruvate, two metabolites derived from the pentose phosphate cycle and glycolysis, respectively. Shikimate is further converted to chorismate by addition of a unit... 

The amino acids possessing an aromatic cycle (tyrosine, phenylalanine, trytophan) are derived from erythrose 4-phosphate and phos-phoenolpyruvate. These two compounds are intermediaries of the pentose cycle and glycolysis, respectively. Their condensation forms shikimate. The condensation of this compound with another molecule of phosphoenolpyruvate produces chorismate, a precursor of aromatic amino acids. 

Q3. Since insects do not have chorismic acid available, both compounds must be derived from tyrosine. 

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