5-Phosphoshikimic acid

In the synthesis of racemic 3-phosphoshikimic acid derivatives a palladium-catalyzed rearrangement of a cyclohexenyl phosphate was used for the stereochemical control of the C-3 oxygen function29. This rearrangement is considerably slower than the analogous reactions of allylic acetates and requires a stoichiometric amount of bis(acetonitrile)palladium(II) chloride. 

The failure of 3-phosphoshikimic acid to be utilized by bacteria is in line with the general inability of intact cells to take up phosphate esters. Its utilization by cell-free extracts of suitable mutants shows it to be an essential intermediate in the common portion of the shikimate pathway. 

The further metabolic changes undergone by shikimic acid are not yet clear. Mutants have been found that excrete two derivatives of shikimic acid (192). One of these, Zl, tentatively identified as a cyclic acetal of shikimic acid with pyruvic acid (192), may be a precursor of prephenic acid (191a). The other, Z2, is a phosphoshikimic acid, and possibly, but not yet certainly, is a normal metabolite succeeding shikimic acid in the chain. 

During the elucidation of the aromatic biosynthetic pathway, compounds were found that appear to be made in side reactions. These include quinic acid, which is reversibly made from dehydroquinic acid through the action of a DPN-specific dehydrogenase. This enzyme is found in Aerobacter, but not in E. coli. 5-Phosphoshikimic acid is also accumulated by certain coli mutants, but has no known metabolic func-... 

Beyond shikimic acid three compounds were detected in culture filtrates that are themselves completely devoid of growth-promoting activity, but which yield growth factors on being autoclaved. One of these was foimd to yield shikimic acid on acid hydrolysis g08). On isolation this compound was identified as being 5-phosphoshikimic acid. The position of the phosphate group was established by exclusion of the other possible positions. The compound is completely hydrolyzed by potato phosphatase to shikimic acid and phosphate. The reason it is not a growth... 

The second inactive compound also yields shikimic acid on heating in acid. It is more labile than 5-phosphoshikimic acid. Its nature remains unknown except for the fact that it probably possesses an organic radical attached to shikimic acid. 

The shikimic acid pathway begins with phosphoenolpyruvate which is obtained from glycolysis, and D-erythrose-4-phosphate, which comes from the pentose phosphate cycle. The two are linked to form an intermediate with 7 C atoms which cyclizes to 5-dehydroquinic acid. The latter exists in equilibrium with quinic acid. The pathway proceeds via 5-dehydroshikimic acid and shikimic acid to 5-phosphoshikimic acid. An additional phosphoenolpyruvate unit is now attached to the last-mentioned compound. The product of this reaction is converted, in several steps, to chorismic acid. 

This route, often called the shikimic acid pathway involves the condensation of phosphoenolpyruvate (2) and a 4-carbon sugar erythrose-4-phosphate (1) which is derived from the pentose phosphate pathway. The product of this reaction is converted to shikimic acid (3). Phosphorylation of shikimic acid to yield 5-phosphoshikimic acid (4) is followed by the addition of another molecule of phospho-enol pyruvate (2) which results in the synthesis of prephenic acid (5). Aromatization of the prephenic acid can give rise to phenylpyruvic acid (6) which upon transamination becomes phenylalanine. The carbon skeletons of the other aromatic amino acids, tryptophane and tyrosine are also synthesised via the shikimic acid pathway as is lignin and many of the aromatic secondary products described in Chapter 6. 

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. 

Permeability barriers were implicated by the failure of dehydroquinic acid to promote growth of mutants blocked before it, by the partial inactivity of shikimate, and also of phosphoshikimate 207, 212). 

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