Chorismate synthesis

With the exception of chorismate synthase [Fig. 2 (7)] all enzymes leading to chorismate synthesis shown in the pathway in Fig. 2 have been demonstrated in plants (Table I). While there is little doubt the pathway shown in Fig. 2 or one very similar to it functions in higher plants there are several pathway relationships yet to be elucidated as will become evident in the discussion which follows. 

End-product inhibition of AS activity by tryptophan appears to be a rather common control mechanism among microorganisms. Nester and Jensen [71] described tryptophan inhibition of B. subtilis AS activity as the first step in sequential feedback control. Excess tryptophan would result in inhibition of the conversion of chorismate to anthrani-late. The consequent accumulation of chorismic acid would then serve as a feedback inhibitor of the DAMPS, the first enzyme in the pathway leading to chorismate synthesis. Bacillus alvei has an anthranilate synthetase which is extremely sensitive to inhibition by tryptophan [98]. In contrast to the mode of AS feedback inhibition in E. coli and S. typhimurium, the B. alvei AS is inhibited by tryptophan noncom-petitively with respect to chorismate and uncompetitively with respect to glutamine. It is the only Bacillus species, among 21 studied, which did not exhibit a sequential feedback control pattern [79]. 

With hydroxy lactone 26 in hand, we were intrigued by the possibility of carrying out a 1,4-elimination of the C-3 hydroxyl, in imitation of the biosynthetic transformation in chorismate synthesis. We have so far been unsuccessful in this endeavor, however, obtaining (not too surprisingly) primarily aromatic materials under a variety of conditions. Both Berchtold and Ganem have reported total syntheses of chorismic acid. 

Inhibition of Chorismate Synthase Shikimic and quinic acids are used by microorganisms, fungi, and superior plants for the synthesis of essential aromatic amino acids from acyclic sugars. Fluorinated analogues of substrates and reaction intermediates have been synthesized in order to inhibit enzymes involved in... 

Wood, H. B. Ganem, B. Short Chemical Synthesis of (-)-Chorismic Acid from (-)-Shikimic Acid, J. Am. Chem. Soc. 1990,112, 8907. 

HGURE 22-16 Biosynthesis of chorismate, an intermediate in the synthesis of aromatic amino acids in bacteria and plants. 

Chorismate Is a Key Intermediate in the Synthesis of Tryptophan, Phenylalanine, and Tyrosine... 

Labeling experiments have shown that the plasto-quinones of chloroplasts as well as the tocopherols each bear one methyl group (marked with an asterisk in Fig. 25-4) that originates from chorismate. The dihydroxy compound homogentisate is probably an intermediate.80 83 It is a normal catabolite of tyrosine in the animal body (Fig. 25-5, Eq. 18-49). Both pren-ylation and methylation by AdoMet are required to complete the synthesis of the plastoquinones and tocopherols. Possible biosynthetic intermediates with one or more double bonds in the polyprenyl side chain have been found in plants and also in fish oils.83a... 

The vitamins K and other naphthoquinones arise from O-succinylbenzoate84 86 whose synthesis from chorismate and 2-oxoglutarate depends upon a thiamine diphosphate-bound intermediate, as indicated in Fig. 25-4. Elimination of pyruvate yields O-succinylbenzoate. The remaining reactions of decarboxylation, methylation, and prenylation (Fig. 25-4) resemble those of ubiquinone synthesis. 

Insertion into an O—H bond is generally favored over cyclopropanation, and consequently protection of hydroxy functionality is normally required. The ease of O—H insertion is nicely illustrated in a recent synthesis of chorismic acid derivatives, where the alkene functionality in (20) was totally unaffected by the carbenoid (Scheme 4).48... 

Until pyruvates. In connection with a synthesis of chorismic acid (1) McGowan and Hcrchiold1 developed a new synthesis of cnol pyruvates, as outlined in chart (I). 

Scheme 6.4.2. Chorismate and isochorismate as branch points toward the synthesis of many different primary and secondary metabolites.

Campbell, M.M. et al. The Biosynthesis and Synthesis of Shikimic Acid, Chorismic Acid, and Related Compounds. 1993 [45]... 

The exbB mutants (47) are derepressed in enterobactin synthesis and produce this siderophore in iron-containing media. The means whereby iron represses enterobactin synthesis is still obscure. Several years ago it was noted that growth of E. coli on low iron media led to changes in various fRNAs (77). In E. coli K-12 aromatic amino-acid synthesizing enzymes are also derepressed in low iron media, possibly because of the diversion of the chorismate pool to enterobactin (78). 

The biosynthetic pathway from SA into L-Phe [69, 70] is shown in Fig. 8.15. The synthesis of chorismate (CHA), the common intermediate in the biosynthesis of the aromatic amino acids, requires an extra equivalent of PEP, which limits the yield of L-Phe from glucose to 0.30 mol mol-1 if PEP is not conserved [91]. The further transformation of CHA into phenylpyruvic acid (PPY) suffers from inhibition by L-Phe and is also subject to transcriptional control [69, 92]. The final step is a reductive amination of PPY into L-Phe with consumption of l-G1u. 

The quinone ring is derived from isochorismic acid, formed by isomerization of chorismic acid, an intermediate in the shikirnic acid pathway for synthesis of the aromatic amino acids. The first intermediate unique to menaquinone formation is o-succinyl benzoate, which is formed by a thiamin pyrophosphate-dependent condensation between 2-oxoglutarate and chorismic acid. The reaction catalyzed by o-succinylbenzoate synthetase is a complex one, involving initially the formation of the succinic semialdehyde-thiamin diphosphate complex by decarboxylation of 2-oxoglutarate, then addition of the succinyl moiety to isochorismate, followed by removal of the pyruvoyl side chain and the hydroxyl group of isochorismate. 

Epoxide opening by benzeneselenolate anion gave the rphenyl selenide with high regioselectivity (Table 8, entry 4)22. Oxidation and rearrangement yielded (+)- ra/t. -2-cyclohexene-1,4-diol. A similar approach was the key step in the synthesis of a ( + )-chorismate-prephenate analog (Table 8, entry 5)24. 

Figure 24.17. Synthesis of Phenylalanine and Tyrosine. Chorismate can be converted into prephenate, which is subsequently converted into phenylalanine and tyrosine. 

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