Double-Ring Epimerization in the Biosynthesis of Clavulanic Acid.

摘要: All reaction steps during the biosynthesis of suicidal clavulanic acid (coformulated with β-lactam antibiotics and used to fight bacterial infections) are known, except for crucial 3S,5S → 3R,5R double epimerization needed produce a biologically active stereoisomer, which mechanistic hypothesis is subject debate. In this work, we provide evidence channel inversion configuration that involves total six steps. When mediated by an enzyme terminal S-H bond, highly complex spontaneous in absence solvents. Polarizable continuum models introduce barriers aqueous environments because strong destabilization first transition state. Molecular geometries electronic structures both cases indicate solvent-free spontaneity medium firmly rooted substantial reorganization electron density right at onset reaction, mostly involving cyclic evolution/involution large regions π delocalization stabilize excess charge left after initial proton abstraction.