Heptulosonic

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]. 

Deoxy-i>maw f)-2-octulosonic acid 8-phosphate can be obtained in gram quantities by using KDO synthase (F.C 4.1.2.16) for the addition of PEP to D-arabinose 5-phosphate33. DA HP synthase (EC 4.1.2.15) produces 3-deoxy-L>-arer/>/>io-heptulosonic acid 7-phosphate from PEP and D-erythrose 4-phosphate35. 

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). 

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. 

In related work, Rutjes and co-workers reported a four-step protocol from conveniently protected sugar derivatives to substituted C-l glycals (Scheme 16).77 The key step in their synthetic route included RCM of highly functionalized a-alkoxyacrylates. The potential of these glycal derivatives was illustrated by their conversion to natural products such as DAH (3-deoxy-D-arabino-2-heptulosonic acid) or KDO (3-deoxy-D-manno-2-ulosonic acid). 

The TBA assay for 3-deoxyglyc-2-ulosonic acids, used by Weissbach and Hurwitz11 to determine 3-deoxy-D-arabino-2-heptulosonic acid, was subsequently applied by Warren13 and by Aminoff14 to the analysis ofN-acetylneuraminic acid (NeuAc, 5 see Fig. 4). The formation of the 3-formylpyruvate-derived chromophore 4 in the periodate... 

Deoxy-araWno-heptulosonic acid 7-phosphate (10) is a metabolic intermediate before shikimic acid in the biosynthetic pathway to aromatic amino-acids in bacteria and plants. While (10) is formed enzymically from erythrose 4-phosphate (11) and phosphoenol pyruvate, a one-step chemical synthesis from (11) and oxalacetate has now been published.36 The synthesis takes place at room temperature and neutral pH... 

Propanediol. In its racemic form, 1,2-propanediol is a petroleum-based high-volume chemical with an aimual production of over 500,0001, mostly used to manufacture the unsaturated polyester resins, yet also featuring excellent antifreeze properties. Enantiomerically pure (/ )-1,2-propanediol accumulates along two different pathways via DAHP (3-deoxy-D-flrahmo-heptulosonic acid 7-phosphate) and methylglyoxal, which then is reduced with either... 

Deoxy-D-araZu o-heptulosonate-7-phosphate synthetase (DAHPS) is the initial enzyme in the pathway responsible for the synthesis of aromatic compounds in microorganisms and plants. It catalyses the reaction shown in Equation (4) ... 

The efficiency of this strategy for the synthesis of 3-deoxy-D-arajblno-2-heptulosonates is outlined in Scheme 12 (51). ... 

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 1. Hypothetical mechanism for shuttling of intermediates of the common aromatic pathway between plastidic and cytosolic compartments. Enzymes denoted with an asterisk (DAHP synthase-Co, chorismate mutase-2, and cytosolic anthranilate synthase) have been demonstrated to be isozymes located in the cytosol. DAHP molecules from the cytosol are shown to be shuttled into the plastid compartment in exchange for EPSP molecules synthesized within the plastid. Abbreviations C3, phosphoenolpyruvate C4, erythrose 4-P DAHP, 3-deoxy-D-arabino-heptulosonate 7-phosphate EPSP, 5-enolpyruvylshikimate 3-phosphate CHA, chorismate ANT, anthranilate TRP, L-tryptophan PPA, prephenate AGN, L-arogenate TYR, L-tyrosine and PHE, L-phenylalanine.

Figure 4. Reactions catalyzed by the broad-specificity DAHP synthase-Co of higher plant cytosol. Condensation of PEP and erythrose 4-P (top) yields 3-deoxy-D-arabino-heptulosonate 7-P (DAHP), whereas condensation of PEP and D-glyceraldehyde 3-P (G-3-P) yields 2-keto-3-deoxy-D-threo-hexulosonate 6-P (DTHP).

Accordingly, a strain of E. coli was first engineered to produce elevated levels of DHQ by increasing the levels of certain key enzymes transketolase, 3-deoxy-D-arabino-heptulosonic acid 7-phospate (DAHP) synthase, and DHQ synthase. Also, the strain has reduced levels of DHQ dehydratase, which if present would divert some of the metabolic flow into the biosynthesis of aromatic amino acids its blockage results in higher production of quinic acid. 

The products obtained from the deamination of 3-amino-3-deoxyheptonic acids were not obtained pure.198 Oxidation of the products gave acids whose calcium salts had elemental analyses agreeing with those calculated lor the calcium salts of pentaric acids, and Shafizadeh2 suggested that the latter are formed from 3-deoxy-2-heptulosonic acids, which, in turn, result from a rearrangement accompanying deamination. 

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). 

R. Ramage, A. M. MacLeod, and G. W. Rose, Dioxolanes as synthetic intermediates. Part 6. Synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO), 3-deoxy-D-araMiio-2-heptulosonic acid (DAH) and 2-keto-3-deoxy-D-gluconic acid (KDG), Tetrahedron 47 5625 (1991). 

The six-carbon chain of ManNAc 6-P can be extended by three carbon atoms using an aldol-type condensation with a three-carbon fragment from PEP (Eq. 20-7, step c) to give N-acetylneuraminic acid (sialic acid).48 Tire nine-carbon chain of this molecule can cyclize to form a pair of anomers with 6-membered rings as shown in Eq. 20-7. In a similar manner, arabi-nose 5-P is converted to the 8-carbon 3-deoxy-D-manno-octulosonic acid (KDO) (Fig. 4-15), a component of the lipopolysaccharide of gram-negative bacteria (Fig. 8-30), and D-Erythrose 4-P is converted to 3-deoxy-D-arafrmo-heptulosonate 7-P, the first metabolite in the shikimate pathway of aromatic synthesis (Fig. 25-1).48a The arabinose-P used for KDO synthesis is formed by isomerization of D-ribulose 5-P from the pentose phosphate pathway, and erythrose 4-P arises from the same pathway. 

The product of the DAHP synthase, 3-deoxy-D-arabino-heptulosonate 7-phosphate, is shown in its cyclic hemiacetal form at the beginning of Eq. 25-2. Its conversion to 3-dehydroquinate is a multistep process that is catalyzed by a single enzyme, 14/15 which is the product of E. coli gene am B. The elimination of... 

The six carbons of the benzene ring of the aromatic amino acids are derived from the four carbons of erythrose 4-phosphate and two of the three carbons of phosphoenolpyruvate (PEP). The initial step in the pathway (Fig. 25-1, step a) is the condensation of erythrose 4-P with PEP and is catalyzed by 3-deoxy-D-arafrmo-heptulosonate-7-phosphate (DAHP) synthase. Closely analogous to an aldol condensation, the mechanism provides a surprise.10 When PEP containing lsO in the oxygen bridge to the phospho group reacts, the lsO is retained in the eliminated phosphate biochemical intuition would suggest that it should stay in the... 

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