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Updated: May 12, 2026

The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
Published on: February 1, 2018
Engineering the synthetic potential of β-lactam synthetase and the importance of catalytic loop dynamics
Jason W Labonte1, Fumitaka Kudo, Michael F Freeman
1Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD, USA. ; Tel: 410 516 7444.
Abstract:
The 2-azetidinone ring of the Class A and D β-lactamase inhibitor clavulanic acid (1) is synthesized by the ATP-utilizing enzyme β-lactam synthetase (βLS). A hydroxyethyl group attached to C-6 of 1 in the (S) configuration markedly enhances the efficacy of this compound against Class C β-lactamases. Guided by a series of X-ray structures of βLS, we have engineered this enzyme to act upon a methylated substrate analogue to give selectively the (3S)-methyl β-lactam core, which, upon closure of the second ring of the bicyclic system of 1, would lead to the (6S)-methylated clavulanic acid derivative.
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