Shikimate-chorismate pathway

Figure 5 The shikimate-chorismate pathway. DAHP, 3-deoxy-o-arabino-2-heptulosonate-7-phosphate EPSP,...

Amino acid biosynthesis is often regulated by the end products of a given pathway to control the relative amounts of amino acids being produced. Aromatic amino acid biosynthesis thus far is known to be feedback regulated at three points in the shikimate/chorismate pathway. The initial step is catalyzed by 3-deoxy-D-arabino-2-heptulosonate-7-... 

The studies of the origin of GHB in A. bisporus demonstrated the involvement of the shikimate-chorismate pathway (Scheme 102). Labeling experiments showed an efficient incorporation of H- and C-labeled shikimic acid 439,440) and C-labeled chorismic acid 441) into the 4-hydroxyaniline moiety of GHB. It was also demonstrated that in the biochemical shikimate-4-hydroxyaniline conversion in the mushroom, amination occurred at the 4 position of one of the carboxylic acid intermediates [initially assumed to be shikimic acid 439)]. Additionally, the p-aminobenzoic acid, which proved to be 441) the precursor of 4-hydroxyaniline, underwent a decarboxylative hydroxylation catalyzed by a FAD-dependent monooxygenase 4-aminobenzoate hydroxylase in the presence of NAD(P)H and O2. This enzyme from A. bisporus was recently purified to homogeneity by Tsuji et al. 442). 

Miscellaneous Compounds Which May he Derived from the Shikimate-Chorismate Pathway... 

Secondary Metabolites Derived Through the Shikimate-Chorismate Pathway. In The Filamentous Fungi (J.E. Smith and D.R. Berry, eds.) Vol. II, p. 460-473. London E. Arnold. 1976. 

Three different metabolic pathways are known to be involved in the synthesis of different classes of phenolic compounds, namely, (1) (Ce — C3) phenylpropanoid derivatives produced by the shikimate/chorismate pathway (2) side chain elongated phenylpropanoids, flavonoids (Ce - C3 - Cg), and few quinones synthesized by the acetate/malOTiate or polyketide pathway and (3) the aromatic terpenoids synthesized throu the acetate/mevalonate pathway. 

EXAMPLES FROM THE SHIKIMATE-CHORISMATE PATHWAY MORE INSIGHT, LESS PROOF... 

Anthraquinone pigments in madder are biosynthesised by the shikimate (chorismate) pathway, which provides only anthra-9,10-quinones. The starting compound is naphtho-l,4-quinone-2-carboxyhc acid. 

Phenazines — The phenazines are biosynthesized by the shikimic acid pathway, through the intermediate chorismic acid. The process was studied using different strains of Pseudomonas species, the major producers of phenazines. The best-known phenazine, pyocyanine, seems to be produced from the intermediate phenazine-1-carboxylic acid (PCA). Although intensive biochemical studies were done, not all the details and the intermediates of conversion of chorismic acid to PCA are known. In the first step, PCA is N-methylated by a SAM-dependent methyltransferase. The second step is a hydroxylative decarboxylation catalyzed by a flavoprotein monooxygenase dependent on NADH. PCA is also the precursor of phenazine-1-carboxamide and 1-hydroxyphenazine from Pseudomonas species. - - ... 

Claisen rearrangement plays an important part in the biosynthesis of several natural products. For example, the chorismate ion is rearranged to the prephenate ion by the Claisen rearrangement, which is catalysed by the enzyme chorismate mutase. This prephenate ion is a key intermediate in the shikimic acid pathway for the biosynthesis of phenylalanine, tyrosine and many other biologically important natural products. 

Scheme 4.12 Catalytic antibody 1F7 was raised against the transition state analog 28 and possesses modest chorismate mutase activity. It can complement a permissive yeast strain that is auxotrophic for phenylalanine and tyrosine by replacingthe natural enzyme (CM) in the shikimate biosynthetic pathway.

The Claisen rearrangement has attracted special attention because of the pronounced solvent dependence of the reaction [92] and the biochemically important Claisen rearrangement of chorismate to prephenate in the shikimic add pathway [93] (Fig. 12). Both aspects of the reaction have been studied recently using DFT methods. 

The conversion of chorismate into prephenate occurs at a critical point in the shikimic acid pathway the biosynthesis of a variety of aromatics branch off from here. Since CM appears in lower organisms (such as fungi and bacteria) and not in mammals, it is an excellent target for the development of antibacterial and antifungal agents. 

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 quinone ring is derived from isochorismic acid, formed by isomerization of chorismic acid, an intermediate in the shikimic acid pathway for synthesis of the aromatic amino acids. The first intermediate unique to menaquinone formation is o-succinyl benzoate, which is formed by a thitunin pyrophosphate-dependent condensation between 2-oxogluttnate emd chorismic acid. The reaction catalyzed by o-succinylbenzoate synthettise is a complex one, involving initially the formation of the succinic semialdehyde-thiamin diphosphate complex by decarboxylation of 2-oxogluttnate, then addition of the succinyl moiety to isochorismate, followed by removed of the pyruvoyl side chain emd the hydroxyl group of isochorismate. 

Chorismic acid 360 is known to be a key intermediate in the shikimate biosynthetic pathway that bacteria and lower plants use to convert carbohydrates into aromatic compounds. 

Several studies of the biosynthesis of chloramphenicol have led to the conclusion that it is formed via the shikimic acid pathway, specifically from chorismic acid. An arylamine synthetase promotes formation of p-amino-L-phenyl alanine (1 ) 50>51. This product is converted to chloramphenicol (15) by oxidation of the amine function to a nitro group, by hy-droxylation of the benzylic methylene group, reduction of the carboxyl... 

Besides showing the unbranched pathway from erythrose-4-phosphate and phosphoenolpyruvate to shikimic acid. Figure 2L13 also shows the sequence of reactions from shikimic acid to chorismate, the first major branch point in the synthesis of the aromatic amino acids and histidine. The sixth reaction of the shikimic acid pathway is inhibited specifically by glyphosate (see here), which is the active ingredient in the broad spectrum herbicide known as Roundup. 

The unbranched pathways from erythrose-4-phosphate and phosphoenolpyruvate through shikimic acid to chorismate is shown in Figure 21.13. The sixth reaction of the shikimic acid pathway is... 

In 1967 it was shown by Young et al. [84] that 2,3-DHBA in K. pneumoniae and E. coli is produced via the shikimic acid pathway (Fig. 1). Evidence showed that the centra) intermediate chorismic acid, leading to the aromatic amino acid pathways, is also the precursor for 2,3-DHBA. The formation of 2,3-DHBA required NAD, and Mg (Fig. 4)... 

Claisen rearrangement of chorismic acid 1 to prephenic acid 2 (Scheme 1), which is catalyzed by the enzyme chorismate mutase, can be considered as the key step in the biosynthesis of aromatic compounds, that is the so-called shikimic acid pathway. The chair-like transition state geometry 3 was proved by double isotope-labeling experiments [2]. However, in the laboratory this particular reaction can be accelerated not only by enzymes but also by catalytic antibodies [3]. For the generation of such antibodies haptenes such as 4 were used, that is, molecules whose structure is very similar to the transition state of the particular reaction and which are tightly bound by the antibody. 

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 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. 

Chorismate mutase (CM) catalyzes the Claisen rearrangement of chorismate to prephenate in the shikimic acid pathway used in the biosynthesis of aromatic amino acids. It represents a reference enzyme to explore the fundamentals of catalysis and has been the subject of extensive experimental and computational research. These have shown both that catalysis proceeds without covalent binding of the substrate to the enzyme, and that the uncatalyzed reaction in water proceeds by the same mechanism. This makes CM a particularly convenient target for QM/MM studies. 

CioHioOa, Mr 226.19. Crystallizes as a monohydrate, mp. 148-149°C, [a]c -295.5° (HjO). In bacteria, fungi, and higher plants C. is an important intermediate in the biosynthesis of aromatic natural products via the shikimic acid pathway. The biosynthesis proceeds via shikimic acid - shikimic acid 3-phosphate -> 5-0-(l-carboxyvinyl)-shikimic acid 3-phosphate - chorismic acid. 

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. 

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