5-Dehydroshikimate

Some biochemical processes involve alcohol dehydration as a key step An example IS the conversion of a compound called 3 dehydroquimc acid to 3 dehydroshikimic acid... 

Figure 6.4 Directed evolution of KDPGal aldolase for application to whole-cell production of 3-dehydroshikimate...

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

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... 

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... 

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. 

Intermediates in the biosynthetic route are 3-dehydroshikimic acid, protocate-chuic acid and catechol (Scheme 7.16). Optimization of microbial ds,ds-muconic acid synthesis required the expression of three enzymes not typically found in Escherichia coli [42cj. E. coli WNl/pWN2.248 was developed that synthesized 36.8 g of ds,ds-muconic acid in a 22% (mol/mol) yield from glucose after 48 h of culturing under fed-batch fermentor conditions. Optimization of the carbon flow directed into ds,ds-muconic acid biosynthesis and manipulation of enzyme activities were aimed at avoiding accumulation of biosynthetic intermediates. 

Phenylalanine, tyrosine, and tryptophan are synthesized by a common pathway in E. coli (Figure 24.13). The initial step is the condensation of phosphoenolpyruvate (a glycolytic intermediate) with erythrose 4-phosphate (a pentose phosphate pathway intermediate). The resulting seven-carbon open-chain sugar is oxidized, loses its phosphoryl group, and cyclizes to 3-dehydroquinate. Dehydration then yields 3-dehydroshikimate, which is reduced by N ADPH to shikimate. The phosphorylation of shikimate by ATP gives shikimate 3-phosphate, which condenses with a second molecule of phosphoenolpyruvate. The resulting 5-enolpyruvyl intermediate loses its... 

Figure 12 Reactions leading to the formation of 4-hydroxybenzoate. (41) 3-dehydroshikimate (42) shikimate (4) CHA, chorismate (9) prephenate (10) 4-hydroxyphenylpyruvate (12) tyrosine (43) 4-hydroxyphenyllactate (44) 4-hydroxycinnamate or 4-coumarate (45) 4-coumaroyl-CoA (46) /3-hydroxythioester of 4-coumaroyl-CoA (47) acetyl-CoA. (48) 4-hydroxybenzaldehyde (4-HBA) (11) 4-hydroxybenzoate (4-HB).

Further information was gleaned from feeding [l- C]glucose. ° This compound was found to label only C-1 and C-10 of the C7N unit, a labelling pattern which is similar to that observed in shikimic acid (191) formed from [1- C]glucose. Neither shikimic acid, however, nor the labelled aromatic amino-acids tested were found to be precursors for the C7N unit of rifamycin S. This does not, of course, exclude earlier intermediates on the shikimate pathway and it was suggested that 3-dehydroquinate (189) or 3-dehydroshikimate (192) may be the key intermediate in the biosynthesis of this unit in rifamycin S (193). 

---