Jump to main content
Jump to site search

Issue 8, 2012
Previous Article Next Article

Engineering the synthetic potential of β-lactam synthetase and the importance of catalytic loop dynamics

Author affiliations

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.

Graphical abstract: Engineering the synthetic potential of β-lactam synthetase and the importance of catalytic loop dynamics

Back to tab navigation

Supplementary files

Publication details

The article was received on 13 Dec 2011, accepted on 10 Jan 2012 and first published on 25 Jan 2012


Article type: Concise Article
DOI: 10.1039/C2MD00305H
Med. Chem. Commun., 2012,3, 960-966

  •   Request permissions

    Engineering the synthetic potential of β-lactam synthetase and the importance of catalytic loop dynamics

    J. W. Labonte, F. Kudo, M. F. Freeman, M. L. Raber and C. A. Townsend, Med. Chem. Commun., 2012, 3, 960
    DOI: 10.1039/C2MD00305H

Search articles by author

Spotlight

Advertisements