Enolpyruvyl shikimate-3-phosphate

This enzyme [EC 4.6.1.4], also known as 5-enolpyruvyl-shikimate-3-phosphate phospholyase, catalyzes the conversion of 5-0-(l-carboxyvinyl)-3-phosphoshikimate to chorismate and orthophosphate, ft should be noted that shikimate is numbered so that the double bond is between Cl and C2. However, some of the early reports on this enzyme numbered shikimate in the reverse direction. 

Aromatic Amino Acid Biosynthesis. The shikimate pathway is the biosynthetic route to the aromatic amino acids tryptophan, tyrosine and phenylalanine as well as a large number of secondary metabolites such as flavonoids, anthocyanins, auxins and alkaloids. One enzyme in this pathway is 5-enolpyruvyl shikimate-3-phosphate synthase (EPSP synthase) (Figure 2.9). 

The mode of action is by inhibiting 5-enolpyruvyl-shikimate-3-phosphate synthase. Roundup shuts down the production of the aromatic amino acids phenylalanine, tyrosine, and tryptophane (30). Whereas all these amino acids are essential to the survival of the plant, tryptophane is especially important because it is the progenitor for indole-3-acetic acid, or auxin, which plays an important role in growth and development, and controls cell extension and organogenesis. 

Inhibits 5-enolpyruvyl-shikimate-3-phosphate synthase (EPSPS), an enzyme of the aromatic acid and biosynthesis pathway. This prevents synthesis of essential aromatic amino acids needed for protein biosynthesis... 

It is now well established that the primary metabolic target of glyphosate is an enzyme of the shikimic acid metabolic pathway, enolpyruvyl shikimate-3-phosphate synthase (2.f ). Via this action, glyphosate blocks the synthesis of the end products of this pathway, notably phenylalanine and tryptophan, but also various subsequent products (Figure 1) ( ,i). It has seemed logical to conclude that the herbicidal effect of glyphosate is a direct result of its effect on the shikimic acid pathway. 

Comparable studies have been performed for the formation of m-cyclo-hexyl fatty acids in Alicydobacillus acidocaldarius and the pathways are identical [100]. A recent publication concerning this later pathway has shown that the final remaining stereochemical ambiguity, the stereochemistry of proton loss at C-6 in the initial 1,4-conjugate elimination of shikimate occurs with loss of the pro-6R proton [102]. This mirrors the stereochemistry of normal shikimate metabolism in the formation of chorismate from 5-enolpyruvyl-shikimate 3-phosphate. 

RR soybean was developed using a glyphosate insensitive CP4-EPSPS (5-enolpyruvyl shikimate 3-phosphate synthase). Since its introduction in 1996, RR soybean has increased steadily from 2 to 89% of the total soybean acres grown in 2005 (Fig. 6.1.2). The widespread adoption of RR soybeans has resulted in significant grower and environmental benefits. In 2004 alone, RR soybeans reduced grower production costs by 1.37 billion and pesticide use by 22.4 million pounds. Furthermore, there has been about a 64% increase in the number of no-till soybean acres that decreased soil erosion, dust and pesticide run-off, and improved soil moisture, air and water quality [2]. 

Mechanism of enolpyruvyl shikimate 3-phosphate synthase exchange of phosphoenolpyruvate with solvent protons. Biochemistry 22 5903-5908. 

Fig. 15.2 Biosynthetic pathway of ubiquinone in prokaryotes. Enzyme names and intermediates are inferred from research studies in E. coli. The chain length of isoprenoids tmd ubiquinone pathway intermediates is kept unspecified (n) to generalize the pathway model to encompass all prokaryotes. (1) eiythtose-4-phosphate (2) phosphoenolpyruvate (3) 3-deoxy-ttfabino-heptulosonate 7-phosphate (4) 3-dehydroquinate (5) 3-dehydroshikimate (6) shikimate (7) shikimate-3-phos-phate (8) 5-enolpyruvyl-shikimate-3-phosphate (9) chorismate (10) para hydroxybenzoate (11) pyruvate (12) glyceraldehyde-3-phosphate (13) l-deoxy-D-xyMose-5-phosphate (14) 2-C-methyl-D-eiythrithol-5-phosphate (15) 4-diphosphocytidyl-2C-methyl-D-erythritol (16) 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate (17) 2-C-methyl-D-erythritol-2,4-cyclo-diphosphate (18) l-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (19) demethylaUyl diphosphate (20) isopentenyl diphosphate (21) farnesyl diphosphate (22) polyprenyl diphosphate (23) 3-polyprenyl-4-hydrobenzoate (24) 2-polyprenylphenol (25) 2-polypienyl-6-hydtoxyphenol ...

A number of analogues that mimic the intermediate formed during the EPSP nthase conversion of shikimic-3-phosphate into EPSP (5-enolpyruvyl shikimate-3-phosphate) have been prepared and tested as inhibitors of the enzyme. The best was shown to be 63. (Z)-3-Fluoro-phosphoenolpyruvate functions as a pseudosubstrate for EPSP synthase producing in one step the same adduct 63, but as an isomeric mixture. ... 

STEINRUCKEN, H.C., N. AMRHEIN. 1980. The herbicide glyphosate is a potent inhibitor of 5-enolpyruvyl-shikimic acid 3-phosphate synthase. Biochem. Biophys. Res. Commun. 94 1207-1212. 

Phenylalanine, tyrosine, and tryptophan are synthesized by a common pathway in E. coli (Figure 24.13). The initial step is the condensation of phosphoenolpyruvate (a glycolytic intermediate) with erythrose 4-phosphate (a pentose phosphate pathway intermediate). The resulting seven-carbon open-chain sugar is oxidized, loses its phosphoryl group, and cyclizes to 3-dehydroquinate. Dehydration then yields 3-dehydroshikimate, which is reduced by N ADPH to shikimate. The phosphorylation of shikimate by ATP gives shikimate 3-phosphate, which condenses with a second molecule of phosphoenolpyruvate. The resulting 5-enolpyruvyl intermediate loses its... 

EPSP synthase catalyzes a rare type of reaction in which the intact enolpyruvyl (carboxyvinyl) group is transferred from phosphoenolpyruvate (PEP) to the 5-hydroxyl group of shikimate 3-phosphate (Fig. 6). This type of reaction is encountered in only one other known enz3rmatic process the transfer of the enolpyruvyl group to UDP-N-... 

Enolpyruvylshikimate-3-phosphate (EPSP) synthase (EC 2.5.1.19), also known as 3-phosphoshikimate 1-carboxyvinyltransferase, catalyzes the reversible transfer of the enolpyruvyl group from PEP to shikimate 3-phosphate (Figure 2.2). There is no known cofactor requirement. When purified to homogeneity, bacterial and plant EPSP synthases are monomeric monofunctional proteins of molecular weight 40,000-50,000. " Some fungi have a radically different molecular architecture in which EPSP synthase is part of a pentafunctional polypeptide which also contains the previous four enzymatic activities of the common shikimate pathway, the arom complex. 

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