Shikimate kinase Shikimic acid

Lobner-Olesen, A. Marinus, M.G. Identification of the gene (aroK) encoding shikimic acid kinase I of Escherichia coli. J. BacterioL, 174, 525-529 (1992)... 

The information obtained from the application of glyphosate to complex systems strongly pointed to one of the following three enzymes as the target of the inhibitor in the shikimate pathway shikimate kinase (EC 2.7.1.71), 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase (EC 2.5.1.19), and chorismate synthase (EC 4.6.1.4). Jointly, these three enzymes convert shikimic acid to chorismic acid in a series of interesting reactions >(Fig. 2). A defined system" had therefore to be found in which the conversion of shikimic acid to chorismic acid could be conveniently studied. 

Anthranilic acid (or o-amino-benzoic acid) is an aromatic acid with the formula C H NO, which consists of a substituted benzene ring with two adjacent, or "ortho- functional groups, a carboxylic acid, and an amine (Fig. 14.1). Anthranilic acid is biosynthesized from shikimic acid (for shikimic acid biosynthesis, see Chapter 10) following the chorismic acid-mediated pathway [1]. Based on its biosynthetic mechanism, shikimate is transformed to shikimate 3-phosphate with the consumption of one molecule of ATP, catalyzed by shikimate kinase. 5-Enolpyruvylshikimate-3-phosphate (EPSP) synthase is then catalyze the addition of phosphoenolpyruvate to 3-phospho-shikimate followed by the elimination of phosphate, which leads to EPSP. EPSP is further transformed into chorismate by chorismate synthase. Chorismate reacts with glutamine to afford the final product anthranilate and glutamate pyruvate catalyzed by anthranilate synthase (Fig. 14.1). 

Koshiba, T. Alicyclic acid metabolism in plants. 12. Partial purification and some properties of shikimate kinase from Phaseolus mungo seedlings. Plant Cell Physiol., 20, 803-809 (1979)... 

Schmidt, C.L. Daneel, H.-J. Schultz, G. Buchanan, B.B. Shikimate kinase from spinach chloroplasts. Purification, characterization and regulatory function in aromatic amino acid biosynthesis. Plant Physiol., 93, 758-766 (1990)... 

In B. subtilis the single DAHPS enzyme is repressed most strongly by tyrosine, but maximal repression required the presence of both tyrosine and phenylalanine [121]. Tryptophan appeared to play no role in repression eontrol of synthesis of the enzyme. Nester et al. [121] also reported that a mixture of the three aromatic amino acids repressed synthesis of DAHPS, dehydroquinate synthetase, and shikimate kinase noncoordinately, but had no effect on the level of dehydroquinase. 

Deoxy-D-arabinoheptulosonic acid-7-phosphate (DAHP) synthase 2 5-dehydroquinate synthase 3 quinate dehydrogenase 4 5-dehydroquinate dehydratase 5 shikimate dehydrogenase 6 shikimate kinase 7 3-enolpyruvylshikimate-5-phosphate synthase 8 chorismate synthase... 

Next (cf. Scheme 11.81), the 3-dehydroquinate was shown to undergo dehydration to produce 3-dehydroshikimic acid and reduction (cf. Scheme 11.82) to shiki-mate (shikimate dehydrogenase, EC 1.1.1.25). In the same scheme, a depiction of phosphorylation to 3-phosphoshikimate (shikimate kinase, EC 2.7.1.71) followed and was shown to set the stage for the reaction of the latter with phosphoenol pyruvate under the influence of the enzyme (3-phosphoshikimate 1-carboxyvinyl transferase, EC 2.5.1.19) to yield 5-(l-carboxyvinyl)-3-phosphoshikimate. Finally, with chorismate synthase (EC 4.2.3.5) (Scheme 11.83), the penultimate progenitor of phenylalanine (Phe, F), tyrosine (Tyr, Y), and tryptophan (Trp, W), viz., chorismate, is produced. These processes are shown in detail in Schemes 11.80-11.83 and, in less detail, in Scheme 12.20. 

The synthesis of compound (44) as a potential transition-state analogue inhibitor of isochorismate synthase (IS) has been reported/ Compounds (45) and (46) have been synthesized from the known 6-fluoroshikimic acids (J. Chem. Soc., Chem. Commun., 1989, 1386) by treatment first with shikimate kinase then 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase and shown to be competitive inhibitors of chorismate synthase/ ... 

Phosphorylation of 3-hydroxyl group of shikimate by shikimate kinase (EC 2.7.1.71) with ATP as a cosubstrate initiates the biosynthesis pathway of anthranilic acid [2], This step also presents the first step of the shikimate pathway, which is a metabolic route used by bacteria, fungi, and plants for the biosynthesis of many aromatic products such as lignins, alkaloids, flavonoids, benzoic acid, and plant hormones, in addition to the aromatic amino acids (phenylalaiune, tyrosine, and tryptophan). The sequential EPSP synthesis is catalyzed by EPSP synthase (EC 2.5.1.19) through the addition of phosphoenolpyruvate to 3-phospho-shikimate followed elimination of phosphate. EPSP synthase belongs to the family of transferases, specifically to those transferring aryl... 

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