Mechanistic insights into the bifunctional non-heme iron oxygenase carbapenem synthase by active site saturation mutagenesis.

ABSTRACT: The carbapenem class of β-lactam antibiotics is known for its remarkable potency, antibacterial spectrum, and resistance to β-lactamase-mediated inactivation. While the biosynthesis of structurally "complex" carbapenems, such as thienamycin, share initial biochemical steps with carbapenem-3-carboxylate ("simple" carbapenem), the requisite inversion at C5 and formation of the characteristic α,β-unsaturated carboxylate are different in origin between the two groups. Here, we consider carbapenem synthase, a mechanistically distinct bifunctional non-heme iron α-ketoglutarate-dependent enzyme responsible for the terminal reactions, C5 epimerization and desaturation, in simple carbapenem production. Interestingly, this enzyme accepts two stereoisomeric substrates and transforms each to a common

SUBMITTER: Phelan RM 

PROVIDER: S-EPMC3683866 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature