Dehydroquinate and

This enzyme [EC 4.6.1.3] catalyzes the conversion of 3-deoxy-(2raZ mo-heptulosonate 7-phosphate to form 3-dehydroquinate and orthophosphate. The enzyme requires cobalt and the hydrogen atoms located on C7 of the substrate are retained on C2 of the product. 

Figure 3. Hypothetical alternative enzyme path between 3-dehydroquinate and shikimate. A reversed order of the dehydratase and dehydrogenase steps of the classical pathway (top) would produce the quinate route (bottom).

Phenolic compounds include a wide range of secondary metabolites that are biosynthesised from carbohydrates through the shikimate pathway [14]. This is the biosynthetic route to the aromatic amino acids, phenylalanine, tyrosine, and tryptophan, and only occurs in microorganisms and plants. In the first step, the glycolytic intermediate phosphoenol pyruvate and the pentose phosphate intermediate erythrose-4-phosphate are condensed to 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP), a step catalysed by DAHP synthase. Intermediates of the shikimate pathway are 3-dehydroquinate, shikimate, and chorismate (Fig. 1). Phenylalanine is biosynthesised from chorismate, and from phenylalanine all the phenylpropanoids. Quinate is produced from 3-dehydroquinate and incorporated into chlorogenic and isochlorogenic acids (caffeoyl quinic acids) by combination with caffeic acid. Gallic acid is produced from shikimate. 

Simple benzoic acids are synthesized in plants via the shikimate pathway, which is derived from shikimic acid, which is itself derived from quinic acid via 3-dehydroquinic and 3-dehydroshikimic acids (Scheme 68.1). In fact, shikimic, but not quinic, acid has been described in the leaves and stems of this species [14]. The simplest benzoic acids are protocatechuic acid (3,4-dihydroxybenzoic acid) and gallic acid (3,4,5-trihydroxybenzoic acid). The latter proved to be present in the tissues of C. roseus, in addition to vanillic acid (4-hydroxy-3-methoxybenzoic acid) [15]. The quantitative composition of C. roseus in benzoic acids can be seen in Table 68.1, and the structures of these compounds are represented in Fig. 68.1. 

Fig. 13.6 New biochemical production route to shikimate from chlorogenate in plant origins is proposed via 3-dehydroquinate and 3-dehydroshikimate. (Reprinted with permission by courtesy...

Dehydroquinic acid and [l,6-14C]-D-shikimic acid methyl ester were not incorporated, indicating a very early branch from the shikimate pathway. The intermediacy of 4-amino-3,4-dideoxy-D-araf>ino-heptulosonic acid 7-phosphate (37) was proposed, consistent with later findings on the role of the variant aminoshikimate pathway [94]. 

Figure 1. Schematic outline of various products and associated enzymes from the shikimate and phenolic pathways in plants (and some microorganisms). Enzymes (1) 3-deoxy-2-oxo-D-arabino-heptulosate-7-phosphate synthase (2) 5-dehydroquinate synthase (3) shikimate dehydrogenase (4) shikimate kinase (5) 5-enol-pyruvylshikimate-3-phosphate synthase (6) chorismate synthase (7) chorismate mutase (8) prephenate dehydrogenase (9) tyrosine aminotransferase (10) prephenate dehydratase (11) phenylalanine aminotransferase (12) anthranilate synthase (13) tryptophan synthase (14) phenylalanine ammonia-lyase (15) tyrosine ammonia-lyase and (16) polyphenol oxidase. (From ACS Symposium Series No. 181, 1982) (62).

This enzyme [EC 4.2.1.10] catalyzes the reaction of 3-dehydroquinate to produce 3-dehydroshikimate and water. 

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... 

Inhibition of Dehydroquinase Type II Dehydroquinase type II is an important enzyme in the shikimic and quinic routes. It ensures the reversible conversion of 3-dehydroquinate (DHQ) into 3-dehydroshrkimate (DHS). Ehmination of the hydroxyl is assisted by an acid/base catalysis that is associated with a residue of the active site. 

The enolate involved in the conversion of 3-dehydroquinate into 3-dehydroshiki-mate can be sterically and electronically mimicked by a vinyl fluoride. However, the ketonization process is impossible. This vinyl fluoride is a competitive inhibitor of dehydroquinase II that is 20 times more powerful than the nonfluorinated analogue (Figure 7.7). Moreover, it is very selective toward dehydroquinase I, whUe it acts according to a different mechanism. ... 

Dehydration of 3-dehydroquinate (step c), the first step in Eq. 25-3, is the first of three elimination reactions needed to generate the benzene ring of the end products. This dehydration is facilitated by the presence of the carbonyl group. After reduction of the product to shikimate (step d)19 a phosphorylation reaction (step e)20,21 sets the stage for the future elimination of Pj. In step/, condensation with PEP adds three carbon atoms that will become the a, P, and... 

Quinic acid, a compound accumulated by many green plants, can be formed by reduction of 3-dehy-droquinate (Eq. 25-2) in both plants and bacteria. Quinic acid can be converted into useful industrial products such as benzoquinone and hydroquinone, and its production by bacteria provides a convenient route to these compounds.168 In the main shikimate pathway 3-dehydroquinate is dehydrated to 3-dehydroshikimate (Eq. 25-3). The latter can be dehydrated... 

TDP-streptose Biosynthesis and 5-Dehydroquinic Acid Synthetase The question mark in the above title should indicate that the next two examples are only a tempting, though hopefully constructive, speculation to demonstrate that TDP-streptose biosynthesis as well as 5-dehydro-quinic synthetase are possible candidates for this group of enzymes with identical initiation of enzyme catalysis by hydrogen transfer to form enzyme-NADH. 

The shikimate pathway is common to both plants and microorganisms (Figure 3-3). Shikimate is synthesized from the substrates phosphoewo/pyruvate (3.9) and erythrose 4-phosphate (3.17). These two precursors are derived from glycolysis and the pentose phosphate pathway, respectively, and are condensed to 3-deoxy-D-ara6/ o-heptulosonate 7-phosphate (DAHP 3.18) by the enzyme DAHP synthase. The subsequent steps result in the formation of 3-dehydro-quinate (3.19) by the enzyme 3-dehydroquinate synthase, 3-dehydroshikimate... 

Fourthly, biotransformations have been used for the synthesis of 3-deoxy-2-glyculosonic acids, using whole cells or purified enzymes. For instance, 3-deoxy-D-araZu rao-heptulosonic acid (DAH) and its 7-phosphate (DAHP, 122) have been produced directly from D-glucose by mutants of E. coli JB-5, that lack dehydroquinate synthase, the enzyme that converts DAHP into the cyclic intermediate dehydroquinic acid (DHQ, Scheme 14). Both DAH and DAHP are secreted into the medium. The dephosphorylated product could be generated in vivo by a phosphatase acting on DAHP.312... 

S. L. Rotenberg and D. B. Sprinson, Isotope effects in 3-dehydroquinate synthase and dehydratase. Mechanistic implications, J. Biol. Chem., 253 (1978) 2210-2215. 

FIGURE 3.2 The common aromatic pathway to chorismate in Escherichia coli K12, where 5 is phosphoe-nolpyruvate, 6 is erythrose 4-phosphate, 7 is 3-deoxy-D-arabinoheptulose 7-phosphate, 8 is 3-dehydroquinic acid, 9 is 3-dehydroshikimic acid, 10 is shikimic acid, 11 is shikimic acid 3-phosphate, and 12 is 5-enolpyru-vylshikimic acid 3-phosphate. 

PEP) shikimate is biosynthesized via 3-deoxy-D-arafeino-heptulosonate 7-phosphate (DAHP), dehydroquinate (DHQ), and dehydroshikimate (DHS) (Scheme 6.4.1). 

Fig. 4-2. Simplified reaction route illustrating the formation of lignin precursors. 1, 5-Dehydroquinic acid 2, shikimic acid 3, phenylpyruvic acid 4, phenylalanine 5, cinnamic acid 6, ferulic acid (Ri=H and R2=OCH3), sinapic acid (R,= R2=OCH3), and p-coumaric acid (R1=R2 = H) 7, coniferyl alcohol (Ri = H and R2=OCH3), sinapyl alcohol (Rj = R2=OCH3), and p-coumaryl alcohol (R =R2=H) 8, the corresponding glucosides of 7.

This product is dehydroquinic acid and is an intermediate on the way to shikimic acid. It is also in equilibrium with quinic acid, which is not an intermediate on the pathway but which appears in some natural products like the coffee ester caffeyl quinic acid. 

In a very imaginative piece of research Frost and coworkers have developed a plasmid-based method for synthesizing aromatic amino acids, by incorporating the genes that code for the enzymes that perform the series of conversions from D-fructose-6-phosphate to D-erythrose-4-phosphate to 3-deoxy-D-arabinoheptulosonic acid-7-phos-phate (DAHP) near each other on a plasmid that can be transformed in E. coli. The enzymes are the thiamin diphosphate-dependent enzyme transketolase in the nonoxida-tive pentose shunt and DAHP synthase. The DAHP is then converted to the cyclic dehydroquinate, a precursor to all aromatic amino acids L-Tyr, L-Phe and L-Trp165,166 (equation 27). 

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