3-deoxy-D-arabino-heptulosonic acid 7-phosphate

Ran, N.Q. and Frost, J. W. (2007) Directed evolution of 2-keto-3-deoxy-6-phosphogalactonate aldolase to replace 3-deoxy-D-arabino-heptulosonic acid 7-phosphate synthase. Journal of the American Chemical Society, 129, 6130-6139. 

J. Frost and J. R. Knowles, 3-Deoxy-D-arabino-heptulosonic acid 7-phosphate Chemical synthesis and isolation from Escherichia coli auxotrophs, Biochemistry 23 4465 (1984). 

The 3-deoxy D-arabino-heptulosonic acid 7-phosphate (DAHP, 34), intermediate of the shikimic acid pathway (cf. Sect. 2.2.4), has also been prepared... 

D. B. Sprinson, J. Rothschild, and M. Sprecher, The synthesis of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate, J. Biol. Chem., 238 (1963) 3170-3175. 

It is proposed that NAD is required for the oxidation of DAMP to a diketone intermediate. The latter compound than undergoes a phosphate elimination yielding a product that undergoes a NADH-dependent reduction to form a dideoxy diketone. This intermediate cyclizes to yield dehydroquinate (Sprinson et al., 1%2 Aldersberg and Sprinson, 1964). Recently, 5-dehydro-3-deoxy-D-arabino-heptulosonic acid 7-phosphate was shown to be an intermediate in the reaction (Maitra and Sprinson, 1978). Sliced sweet potato root and potato tuber tissue show increased DHQ syntlfase activity reminiscent of the injury-stimulated increases in those tissues of phenylalanine ammonia lyase and other enzymes of phenolic biosynthesis (Saijo and Kosuge, 1978). 

The enzyme-catalysed condensation of erythrose and phosphoenol pyruvate leads to 3-deoxy-(D)-arabino-heptulosonic acid 7-phosphate this loses phosphate to give an enol, which cydises to 3-dehydroquinic acid. Aromatisa-tion goes along with the loss of two molecules of water. Finally, a catechol-O-methyltransferase from S-adenosylmethionine (SAME) brings about methyla-tion of the hydroxy-function. Vanillic acid is the end-product obtained from the microorganism. 

When the entire chain of seven common intermediates had been elucidated, the surprising fact emerged that this sequence oscillates back and forth between phosphorylated and phosphorus-free stages. It begins with 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP), continues with the three phosphorus-free metabolites 3-dehydroquinic acid, 3-dehydroshikimic acid, and shikimic acid, proceeds next through the two phosphorylated intermediates shikimic acid 3-phosphate and 5-enolpyruvylshikimic acid 3-phosphate, and ends with the phosphorus-free chorismic acid. 

As part of a major review of enzymic synthesis of carbohydrates, Whitesides and coworkers have discussed the current situation regarding enzjrme-catalysed syntheses of 3-deoxyulosonlc acids, The same group have described the combined enzymatic-chemical route to 3-deoxy-D-arabino-heptulosonic acid-7-phosphate (DAHP,16) outlined in Scheme 6. 5... 

On the basis of FruA-catalyzed aldol reactions 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAFIP, 26), an intermediate of the shikimic acid pathway, has been synthesized from N-acetylaspartic semialdehyde 68 (Figure 5.35) [200]. Precursors to KDO (Section 5.3.2) and its 4-deoxy analog (71) have been prepared by FruA catalysis from aldehydes 70 that incorporate an acrylic moiety for further functionalization [201]. 

Glyphosate also inhibits the activity of a form of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (13), however, this inhibition is relatively weak. Effects of glyphosate on the enzymes of aromatic amino acid synthesis have been described in more detail in recent reviews (14-17). 

Subsequently some doubt was cast on Mechanism D, because it has been shown1578 that the condensation occurs with partial retention of the geometric asymmetry of 0-phosphono-enolpyruvic-3(Z)-f and -3(E)-t acids (48a), so that, from the former, 3-deoxy-D-arabino-heptulosonate-3(S)-t 7-phosphate was the preponderant product. This... 

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. 

Fig. 10. Amino acid homologies between the tyrosine-sensitive and the phenylalanine-sensitive isoenzymes of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Escherichia coli. Reprinted from Reference 28 with permission of the American Society of Biological Chemists.

The nucleotide sequence of the aroF gene of Escherichia coli and the amino acid sequence of the encoded protein, the tyrosine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase. J. 

The metabolic pathway responsible for biosynthesis of aromatic amino acids and for vitamin-like derivatives such as folic acid and ubiquinones is a major enzyme network in nature. In higher plants this pathway plays an even larger role since it is the source of precursors for numerous phenylpropanoid compounds, lignins, auxins, tannins, cyano-genic glycosides and an enormous variety of other secondary metabolites. Such secondary metabolites may originate from the amino acid end products or from intermediates in the pathway (Fig. 1). The aromatic pathway interfaces with carbohydrate metabolism at the reaction catalyzed by 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase, the condensation of erythrose-4-phosphate and PEP to form... 

The first enzyme which is specific for aromatic amino acid biosynthesis is 3-deoxy-D-arabino-heptulosonic 7-phosphate (DAHP) synthase (EC 4.1.2.1.5), which utilizes D-erythrose 4-phosphate (E4P) and phosphoenolpyruvate (PEP) as substrates (Fig. 2). Le Mar chal al.prepared the isosteric homophosphonate of E4P, in which the C-O-P group is replaced by the C-CH2-P group as well as the non-isosteric phosphonate analogue, in which the C-O-P group is replaced by the C-P group (Fig. 3). Both analogues served as substrates for the tyrosine-sensitive DAHP synthase of Escherichia coli, with Vmax values in the ratio 20 3.5 1 for E-4-P, the phosphonate, and the homophosphonate. 

Other pyruvate- and phosphoenolpyruvate-dependent aldolases have been isolated and purified, but have not yet been extensively investigated for synthetic use. Those showing promise for future applications include, 3-deoxy-D-arabino-2-heptulosonic acid 7-phosphate (DAHP) synthetase (EC 4.1.2.15), 2-keto-4-hydroxyglutarate (KHG) aldolase (EC 4.1.2.31), and 2-keto-3-deoxy-D-gluconate (KDG) aldolase (EC 4.1.2.20). DAHP synthetase has been used... 

In extracts of a wild type of E. coli (Strain B), enolpyruvate phosphate and D-erythrose 4-phosphate are converted to a 3-deoxyheptulosonic acid (most probably of the arabino configuration) and two equivalents of orthophosphate. Since 3-deoxy-D-arai fno-heptulosonic acid 7-phosphate was readily dephosphorylated by these enzyme preparations, the conclusion was... 

Deoxy-D-arabino-2-heptulosonic Acid 7-Phosphate (DAHP) Synthetase (E.C. 4.1.2.15)... 

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