Succinylbenzoic acid synthase

The biosynthesis of menaquinones in E. coli (Fig. 5) starts with the conversion of isochorismic acid and a-ketoglutaric acid in the presence of thiamine pyrophosphate [105-107] to 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid (SHCHC) catalyzed by SHCHC synthase, and a-ketoglutarate decarboxylase, both encoded by the menD gene [104,108,109]. SHCHC is converted to o-succinylbenzoic acid by dehydration, catalyzed by a protein encoded by menC (Table 1) [110]. Palaniappan et al., [111] showed for the first time the biosynthesis of menaquinones via o-succinyl benzoic acid in B. subtilis including the activity of the enzymes. 

Formation of the coenzyme A ester of the aliphatic carboxyl group of o-succinylbenzoic acid (38) appears to activate the methylene proton sufficiently to permit attack at the aromatic carboxyl group (Fig. 6.7). 2-Carboxy-4-oxotetra-lone (COT) (43) and/or l,4-dihydroxy-2-naphthoic acid (DHNA) (40) are likely intermediates for later stages of synthesis. The enzymatic conversion to DHNA with naphthoate synthase (which consists of OSB CoA synthetase and DHNA synthetase) requires ATP, Mg ", and coenzyme A. 1,4-Dihy-droxy-2-naphthoic acid (40) is a precursor of vitamin K2 (35) and menaquinones (such as 44) (Inouye and Leistner,... 

This is an important observation because both enzyme systems decarboxylate a-ketoglutarate (III) in the presence of thiamine pyrophosphate generating a carbanion. In the case of the a-ketoglutarate dehydrogenase, the carbanion reduces lipoic acid whereas in the case of the OSB synthase, it attacks iso-chorismic acid (I) (Fig. 1). Elimination of 0H and the pyruvate residue results in aromatization, the first aromatic product being -succinylbenzoic acid (II) (Fig. 1). 

Johnson, T.W., Naithani, S., Zybailov, B., Jones, A.D., Golbeck, J.H., and Chitnis, P.R., The meriD and menE homologues code for 2-succinyl-6-hydroxyl-2,4-cyclohexadiene-l-carboxylate synthase and O-succinylbenzoic acid-CoA hgase in the phylloquinone biosynthetic pathway of Synechocystis sp. PCC 6803, Biochim. Biophys. Acta, 1557, 67, 2003. 

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. 

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... 

Fig. 144. Biosynthesis of naphthoquinone and anthraquinone derivatives from chorismic acid 1 2-Succinylbenzoate synthase 2 2-succinylbenzoate Co A ligase, naphthoate synthase 3 l,4-dihydroxy-2-naphtho-ate polyprenyltransferase...

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