Enzymatic synthesis of monocyclic beta-lactams.
An Mg2+ and ATP dependent beta-lactam synthetase (BLS) catalyses formation of a beta-lactam ring during the biosynthesis of clavulanic acid, an important beta-lactamase inhibitor. An epimeric mixture of a 2-methylated derivative of the natural BLS substrate N2-(2-carboxyethyl)-L-arginine was synthesised and found to be a substrate for the enzyme. The epimeric products were characterised by 1H NMR and mass spectrometric analyses. The results suggest that a modified version of BLS might be used to catalyse the preparation of intermediates useful for the synthesis of beta-lactam antibiotics.
Sleeman
Mark C
MC
The Dyson Perrins Laboratory and the Oxford Centre for Molecular Sciences, South Parks Road, OX1 3QY, Oxford, UK.
MacKinnon
Colin H
CH
Hewitson
Kirsty S
KS
Schofield
Christopher J
CJ
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D013058:Mass Spectrometry; D008997:Monobactams / Q000096:biosynthesis*; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D014170:Transformation, Genetic
D008997:Monobactams; C005394:octopine; D001120:Arginine; D000581:Amidohydrolases; C114020:beta-lactam synthetase