3-Deoxy-D-arabinoheptulosonate

Pyocyanin (160) is derived from the shikimate pathway, and one protein, PhzC, is equivalent to enzymes that catalyze the first step in this pathway, converting erythrose 4-phosphate (162) and phosphoenolpyruvic acid (163) to 3-deoxy-D-arabinoheptulosonate 7-phosphate (164) (Fig. 28). The equivalent enzyme in the shikimate pathway is thought to be feedback regulated, and PhzC is likely to shunt intermediates toward the shikimate pathway in preparation for pyocyanin (160)... 

For the aromatic pathway (Figure 30.20), the critical control points are the condensation of phosphoenolpyruvate and erythrose-4-phosphate to 3-deoxy-D-arabinoheptulosonate 7-phosphate, DAHP, by DAHP synthase. For tryptophan, the formation of anthranilic acid from chorismic acid by anthranilate synthase is the second critical control point. The transcriptional regulation was overcome through the use of alternative promoters and allosteric regulation was circumvented by the classical technique of selection for feedback-resistant mutants using toxic analogues of the repressing compounds. 

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). 

Similarly, the methylene analogue of 3-deoxy-D-arabinoheptulosonic acid 7-phosphate (DAHP) has been prepared from the C7 aldehyde derived from methyl (methyl 3-deoxy-D-arabinoheptulopy-ranosid)onate in 60% yield.The protected 3-dehydroquinate (DHQ) has also been used as starting material in the synthesis of phosphonic DHQ synthase inhibitors by the same methylenediphosphonate approach in 56% yield (Scheme 8.66). Preparation of the phosphonate analogue of porphobilinogen is another illustration of the advantages of this synthetic procedure. ... 

Dehydroquinate synthase catalyzes the j3-elimination of phosphate from 3-deoxy-D-arabinoheptulosonate 7-phosphate (23) to form (26), as a partial reaction during the formation of dehydroquinate (28) [Eq. (60)] ... 

Fig.3. Biosynthesis of chorismic acid. DAMP = 3-deoxy-D-arabinoheptulosonic acid 7-phosphate.

Phosphoenblpyruvic acid (D 2) and erythrose-4-phosphate serve as precursors. 3-Deoxy-D-arabinoheptulosonic acid-7-phosphate is built as a key intermediate. This compound cyclizes to 5-dehydroquinic acid, which is transformed to 5-de-hydroshikimic acid and shikimic acid. After phosphorylation shikimic acid reacts with phosphoenolpyruvate. The formed 3-enolpyruvylshikimic acid-5-phosphate yields chorismic acid by an anti-elimination of a proton and the phosphate group. 

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... 

The biosynthetic pathway through shikimic acid (5.7) to aromatic amino acids, outlined in Scheme 5.1 (acids are shown as anions) is called the shikimic acid or shikimate pathway [1, 2, 5]. It has its origins in carbohydrate metabolism and shows several interesting features, much of it known from detailed examination of the steps involved. The first step is a stereospecific aldol-type condensation between phosphoenolpyruvate (5.7) and D-erythrose-4-phosphate (5.2) to give 3-deoxy-D-arabinoheptulosonic acid 7-phosphate (5.5 DAHP), in which addition occurs to the jz-face of the double bond in (5.7) and the r -face of the carbonyl group in (5.2) and which has been rationalized in terms of the mechanism shown in Scheme 5.2... 

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