Acids shikimic acid

Precursor selection An important step in designing a microbial labeling process is the identification of one or more suitable labeled precursors. Generally, secondary metabolites are biosynthesized via primary metabolites from five metabolic sources. These are amino acids, shikimic acid (shikimic acid pathway), acetate and its homologues (polyketide pathway), mevalonic acid (isoprene pathway) and carbohydrates. Selection of a suitable precursor is primarily influenced by the biosynthetic pathway(s) involved, but also depends on the desired position of label in the product and the availability of labeled precursors. 

The shikimate pathway is the major route in the biosynthesis of ubiquinone, menaquinone, phyloquinone, plastoquinone, and various colored naphthoquinones. The early steps of this process are common with the steps involved in the biosynthesis of phenols, flavonoids, and aromatic amino acids. Shikimic acid is formed in several steps from precursors of carbohydrate metabolism. The key intermediate in quinone biosynthesis via the shikimate pathway is the chorismate. In the case of ubiquinones, the chorismate is converted to para-hydoxybenzoate and then, depending on the organism, the process continues with prenylation, decarboxylation, three hydroxy-lations, and three methylation steps. - ... 

The shikimate pathway begins with a coupling of phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate to give the seven-carbon 3-deoxy-D-arabino-heptulo-sonic acid 7-phosphate (DAHP) through an aldol-type condensation. Elimination of phosphoric acid from DAHP, followed by an intramolecular aldol reaction, generates the first carbocyclic intermediate, 3-dehydroquinic acid. Shikimic acid (394) is... 

N.A. Flavonoids, terpenoids, alkanes, phenolic acids, shikimic acid, chobne." For bronchial asthma, mildly sedative, treats intestinal amebiasis. 

Cinnamic acids are commonly found in plants as esters of quinic acid, shikimic acid, and tartaric acid. For example, chlorogenic acid (1.18) is an ester of caffeic acid and quinic acid. 

The aromatic amino acids, phenylalanine, tryptophan, and tyrosine, are all made from a common intermediate chorismic acid. Chorismic acid is made by the condensation of erythrose-4-phosphate and phosphoenol pyruvate, followed by dephosphorylation and ring closure, dehydration and reduction to give shikimic acid. Shikimic acid is phosphorylated by ATP and condenses with another phosphoenol pyruvate and is then dephosphorylated to give chorismic acid. 

Phenylalanine and tyrosine acts as precursor for opium alkaloid biosynthesis. Tryptophan is a significant source of Vinca alkaloids. Alkaloids are derived from anthranilic acid, which is an intermediate in biosynthesis of tryptophan. Some alkaloids are derived from acetate, terpene or shikimic acid. Shikimic acid is a significant metabolite as most of the aromatic constituents are derived from shikimic acid pathway. 

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... 

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 3-Deoxy-D-araW o-2-heptulosonic acid 7-phosphate - 3-dehydroquinic acid (see quinic acid) - 3-dehydroshikimic acid - shikimic acid. 

A preferable starting material, and the one that for several years now has been used as the source of the commercial drug, is (-)-shikimic acid. Shikimic acid is the plant metabolite that provides the biochemical precursor to the aromatic amino acids such as phenylalanine, tyrosine, and tryptophan. It is abundant in the spice star anise, grown in China, which can yield 3-7% of shikimic acid. 

Because shikimic acid does not enter into mammalian metabolism, its synthesis and use are clear targets at which to aim selective toxicity. In bacteria, shikimic acid arises by cyclization of the carbohydrate 3-deoxy-2-oxo-D- mAzVzoheptulosonic acid 7-phosphate, which is formed by the condensation of erythrose 4-phosphate and phosphoenolpyruvic acid. Shikimic acid undergoes biosynthesis to chorismic acid (4.55) which is the enolpyruvic ether of raw5-3,4-dihydroxy cyclohexa-1,5-diene-1-carboxylic acid. As its name indicates, this acid sits at a metabolic fork, the branches of which lead to prephenic acid, to phenylalanine (and hence to tyrosine), to anthranilic acid (and hence tryptophan), to ubiquinone, vitamin K, and/ -aminobenzoic acid (and hence folic acid). 

As phenolic compounds have been shown to interfere in indole biosynthesis CEef. 3)i the reciprocal, situation, i.e. inhibition of phenolic s thesis by indole compounds (mainly lAA, see belowj, weis considered to occur possibly at the level of PAL. The intermediate products of lAA synthesis, anthranilicoand indolepyruvic acids had a peculiar effect on the HOH formation from the radioactive phenylalanine by first completely repressing the formation and then, after a lag phaae of ca. 90 min, allowing it to proceed at the rate of the control. The common precursor of the aromatic amino acid shikimic acid showed, however, no effect, while the aromatic amino-acids tyrosine and tryptophan caused inhibition. 

Fig. 7.11. Chlorogenic acid, shikimic acid, and quinic acid.

D 8 Derivatiyes of Dehydroquinic Acid, Dehydroshikimic Acid, Shikimic Acid, and Chorismic Acid... 

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. 

Biosynthesis of Dehydroquinic Acid Shikimic Acid and Chorismic Acid (Fig. 143)... 

Before Mrs. Mingioli and I started work on the isolation of a new intermediate, its excretion by suitable mutants was studied by Dr. Davis, who selected the strain which showed the best production of the metabolite. Our research led to the isolation in pure form, and to the complete structure proof, of three new intermediates 3-dehydroquinic acid, shikimic acid 3-phosphate, and prephenic acid. Of these, the last one turned out to be a precursor of phenylalanine and tyrosine only. In contrast, the two other compounds were shown to be intermediates in the biosynthesis of all five primary aromatic metabolites. 

Shikimic Acid, Isoshikimic Acid, and Prephenic Acid. As will be seen in the next chapter (Chapter 12), the amino acids phenylalanine, tyrosine, and tryptophan all contain aryl rings. The biosynthesis of the aromatic rings of these amino acids passes through the same seven-carbon carboxylic acid, shikimic acid, which itself is derived from erythrose and phosphoenolpyruvate. As shown in Scheme 11.10, as part of the... 

The precursors of flavonoid biosynthesis include shikimic acid, phenylalanine, cinnamic acid, and p-coumaric acid. Shikimic acid acts as an intermediate in the biosynthesis of aromatic acid. The basic pathways to the core isoflavonoid skeletons have been established both enzymatically and genetically [16]. The synthesis of isoflavones can be broadly divided into three main synthetic pathways the formylation of deoxybenzoins, the oxidative rearrangement of chalcones and flavanones, and the arylation of a preformed chromanone ring. In leguminous plants, the major isoflavonoids are produced via two branches of the isoflavonoid biosynthetic pathway, and the different branches share a majority of common reactions [1]. Unlike the common flavonoid compotmds, which have a 2-phenyl-benzopyrone core structure, isoflavones, such as daidzein and genistein, are 3-phenyl-benzopyrone compounds. Biochemically, the synthesis of isoflavones is an offshoot of the flavonoids biosynthesis pathway. Several attempts have aimed to increase... 

Aromatic compounds are synthesized from carbohydrate precursors. These form a 7-carbon compound that cyclizes and loses water (or phosphate) and is reduced to shikimic acid. Shikimic acid is converted via unknown intermediates into three groups of compounds. One pathway leads to phenylalanine and tyrosine, the second forms anthranilic acid, which is a precursor of indole, and the third produces p-aminobenzoic acid and related compounds (I). Many of the individual steps in these pathways have been described in the last few years. 

The evidence that (- )-shikimic acid plays a central role in aromatic biosynthesis was obtained by Davis with a variety of nutritionally deficient mutants of Escherichia coli. In one group of mutants with a multiple requirement for L-tyrosine, L-phenylalanine, L-tryptophan and p-aminobenzoic acid and a partial requirement for p-hydroxybenzoic acid, (—)-shikimic acid substituted for all the aromatic compounds. The quintuple requirement for aromatic compounds which these mutants displayed arises from the fact that, besides furnishing a metabolic route to the three aromatic a-amino acids, the shikimate pathway also provides in micro-organisms a means of synthesis of other essential metabolites, and in particular, the various isoprenoid quinones involved in electron transport and the folic acid group of co-enzymes. The biosynthesis of both of these groups of compounds is discussed below. In addition the biosynthesis of a range of structurally diverse metabolites, which are derived from intermediates and occasionally end-products of the pathway, is outlined. These metabolites are restricted to certain types of organism and their function, if any, is in the majority of cases obscure. 

Esters of phenolic acids, particularly the hydroxycinnamic acids (9, 12, 13 and 14), with (—)-quinic acid, (—)-shikimic acid and D-glucose are also widely distributed in the plant kingdon Chlorogenic acid (23), 5-O-caffeoyl-quinic acid, is for example... 

Figure 5.14. Distribution of radioactivity in gallic acid, ( -)-shikimic acid and veratric acid after feeding 6-[ C]-D-glucose and l-[ C]-D-glucose ...

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