O-succinylbenzoate synthase (OSBS)

O-succinylbenzoate synthase (OSBS), also known as MenC, is a member of the enolase superfamily and a key enzyme in the classical menaquinone (Vitamin K2) biosynthetic pathway (UniProt, 2023). It catalyzes the dehydration of 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) to form O-succinylbenzoate, a precursor essential for the production of menaquinone (PubMed, PMID: 15104422). This pathway is vital for the respiratory chains of many pathogenic bacteria, including Mycobacterium tuberculosis and Bacillus anthracis, particularly under anaerobic conditions (PubMed, PMID: 12625847). The NSAR/OSBS family is a classic example of enzyme evolution and promiscuity, where some members exhibit both OSBS and N-succinylamino acid racemase (NSAR) activities (Biochemistry, 1999). Because the menaquinone biosynthetic pathway is absent in humans, OSBS is considered a high-value target for the development of selective antibacterial agents with low host toxicity (Future Medicinal Chemistry, 2020). Experimental inhibitors typically include transition state analogs and substrate mimics designed to block the enzyme active site and halt bacterial energy metabolism.

Other names

MenCN-succinylamino acid racemaseNSAR2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase

Inhibition of the dehydration of 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate to O-succinylbenzoate, disrupting menaquinone synthesis and bacterial ATP production.