o-Succinylbenzoate synthase (OSBS) (OSBS)

o-Succinylbenzoate synthase (OSBS) is a member of the enolase superfamily and a key enzyme in the classical menaquinone (Vitamin K2) biosynthetic pathway found in various bacteria, including Mycobacterium tuberculosis (UniProt, 2024). It catalyzes the dehydration of 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) to produce o-succinylbenzoate (OSB), which is a precursor for the naphthoquinone ring of menaquinone (PubMed, 2022). Since humans lack this biosynthetic pathway and obtain Vitamin K from their diet, OSBS is a promising target for the development of selective antibacterial agents that do not interfere with human metabolism (PubChem, 2023). Inhibition of OSBS disrupts the production of menaquinone, an essential component of the bacterial electron transport chain, leading to a failure in cellular respiration and ATP synthesis (Journal of Biological Chemistry, 2021). While no drugs targeting OSBS are currently FDA-approved, research is active in developing transition-state analogs and other small molecules to combat multi-drug resistant infections (ACS Infectious Diseases, 2020).

Other names

OSB synthaseMenC2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthaseSHCHC synthase

Inhibition of the dehydration of 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate to o-succinylbenzoate, thereby blocking the biosynthesis of menaquinone and disrupting the bacterial electron transport chain.