O-Succinylbenzoate

Menaquinone. The incorporation of [2- C]mevalonate and [2- C]-2-methyl-l,4-naphthoquinone into MK-4, normally considered a bacterial quinone, has been demonstrated in marine invertebrates such as crabs and starfish." Incorporation into 2,3-epoxy-MK-4 (163) was also observed. Cell-free extracts have been prepared from Escherichia coli which catalyse the conversion of o-succinylbenzoic acid (164) into l,4-dihydroxy-2-naphthoic acid (165) and menaquinones. In the presence of farnesyl pyrophosphate the major menaquinone produced was MK-3. Genetic studies with mutants of E. coli K12 that require (164) offer support for the generally accepted pathway for MK biosynthesis via (164) and (165)." The enzyme system that catalyses the attachment of the polyprenyl side-chain to 1,4-dihydroxy-2-naphthoic acid to form demethylmenaquinone-9 (166) has been isolated from E. colU ... 

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. 

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. 

Lack of congruence of sequence and structure with function Common sequence and structure, indeed identity of the protein itself, do not imply a unique function Each pair, o-succinylbenzoate synthase (OSBS)-N-acetylamino acid racemase, and lens crystallin-lactate dehydrogenase, share sequence and structure but differ in function. 

NAAR N-acetylamino acid racemase OSBS O-succinylbenzoate synthase. 

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. 

There are many enzymes in the functionally diverse enolase superfamUy. The overall structural features of these enzymes are similar to the enolase structures, with an aip barrel active domain and a smaller domain (left lower domain. Figure 13A) where the essential Mg(II) bound to two Asp and one Gin side chains on the third, fourth and fifth p strands. In some cases, however, the active domain is better described as an aip)jP barrel (e.g. Figure 14A). The enzymes in this superfamily include O-succinylbenzoate synthase, epimerases, racemases, the muconate and carboxy lactonizing enzymes (cycloiso-merases) in bioconversion of catechol and protocatechuate, respectively , acid-sugar... 

FIGURE 14. (A) Stracture of O-succinylbenzoate synthase of the enolase supeifamily with an aip)qP barrel active-site domain as labeled and an aip domain at the lower-right side (PDB ID IFHV, Plate XXXII). (B) The product O-succinylbenzoate (blue ball-and-stick stmcture in Plate XXXIII) is bound to the active-site Mg(II) via the carboxylate functionality. The structure with a bound substrate 2-succinyl-6-hydroxy-2,4-cyclohexadiene-l-carboxylate (1R6W, red baU-and-stick stmcture in Plate XXXIII) is superimposed onto the stracture IFHV to reveal the difference in binding. One of the coordinated water molecules is replaced by the bidentate carboxylate of the substrate... 

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. 

Figure 11 Non-o-succinylbenzoate (non-OSB) or futalosine pathway for MK biosynthesis. (4) CHA, chorismate (36) inosine (37) C2 unit, Phosphoenolpyruvate (8) futalosine (38) dehypoxanthinylfutalosine (DHFL) (39) cyclic dehypoxanthinylfutalosine (40) 1,4-dihydroxy-6-naphthoate (2) menaquinone. In the MK structure, n = 9 in Streptomyces and n = 8 in Thermus. , uncertain or not definite.

Enolase superfamily MLE o-succinylbenzoate synthase (OSBS) Dehydration of SHOHO (2-succinyl-6R- N-acylaminoacid racemase 13, 132... 

---