Isochorismate

Within the diastereomeric switch sequences, the corresponding trans-diols become accessible either using a Mitsunobu inversion or a reversible Diels-Alder cyclization as key reaction step [249,250]. This synthetic strategy is complementary to an approach involving metabolic engineering of E. coli via the chorismate/ isochorismate pathway [251]. 

This enzyme [EC 5.4.99.6], also known as isochorismate synthase and isochorismate hydroxymutase, catalyzes the interconversion of chorismate and isochorismate. 

COMPUTER ALGORITHMS SOFTWARE ISOCHORISMATE SYNTHASE ISOCITRATE DEHYDROGENASE ISOCITRATE LYASE "ISO-COOP,"... 

The product of step o is known as isochoris-mate.55 56 Isochorismate gives rise to a variety of products including vitamin K, salicylic acid,56a the iron chelator enterobactin (Fig. 16-1), and other siderophores. These are formed in E. coli via 2,3-dihy-droxybenzoate as indicated in Fig. 25-2.57-59a The genes (ent) for the requisite enzymes are clustered at 14 min on the E. coli chromosome map (Fig. 26-4). 

Write out, using structural formulas, a step-by-step reaction sequence for the conversion of O-succinylbenzoate into isochorismate as indicated in Fig. 25-4. 

Figure 3-5. Biosynthesis of salicylic acid. The enzymes involved in this pathway are (a) chorismate mutase (E.C. 5.4.99.5), (b) prephenate aminotransferase (E.C. 2.6.1.78 and E.C. 2.6.1.79), (c) arogenate dehydratase (E.C. 4.2.1.91), (d) phenylalanine ammonia lyase (E.C. 4.3.1.5), (e) presumed P-oxidation by a yet to be identified enzyme, (f) benzoic acid 2-hydroxylase, (g) isochorismate synthase (E. C. 5.4.4.2), and (h) a putative plant pyruvate lyase.

Wildermuth M. C., Dewdney, J., Wu, G., and Ausubel, F. M., 2001, Isochorismate synthase is required to synthesize salicylic acid for plant defence, Nature 414 562-565. 

I indicaxanthin indole-3-acetic acid iridoskyrim isochorismate isoflavone isoorientin 1.67 2.49 2.39 3.43 1.33 6.21... 

Chorismate is formally the last metabolite of the shikimate pathway and serves as a branch point towards different biosynthetic byways (Scheme 6.4.2) [2], From an evolutionary standpoint chorismate was evolved not as a metabolite with a distinct cell function, but rather as a highly flexible building block. Because of the special character of 1,3-cyclohexadiene systems, with only a small energy barrier to aromatization, chorismate and its constitutional isomer isochorismate, which... 

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

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. 

The biosynthesis of menaquinone is outlined in Fig. 44. Isomerization of chorismate to isochorismate followed by condensation with a-ketogluta-rate and aromatization gives o-succinylbenzoic acid. Conversion of 238 to the CoA thio ester, followed by cyclization, prenylation and methylation completes the biosynthesis. The biosynthesis of the prenyl side chain follows the alternative terpene biosynthetic pathway described for ubiquinone. 

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