Interactions between non-classical β-lactam compounds and the β-lactamases of Actinomadura R39 and Streptomyces albus G

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Abstract
6-Aminopenicillanic acid, 7-aminocephalosporanic acid, mecillinam and quinacillin have varying substrate activities for R39 .beta.-lactamase (excreted by Actinomadura R39) and the G .beta.-lactamase (excreted by S. albus G). Cefoxitin and quinacillin sulfone are not recognized by the G .beta.-lactamase and are weak inactivators of the R39 .beta.-lactamase. N-Formimidoylthienamycin is a poor substrate for the G .beta.-lactamase and a potent inactivator of the R39 .beta.-lactamase. The high value of the bimolecular rate constant for enzyme inactivation is mainly due to a very low dissociation constant (1 .mu.M). Clavulanate is an inactivator of both G and R39 .beta.-lactamases. The reaction with this latter enzyme is a branched pathway where normal turnover and permanent enzyme inactivation occur concomitantly. Between 28-43 molecules of clavulanate are hydrolyzed before one of them has the opportunity to inactive 1 molecule of enzyme.