PENICILLIN 3-ALDEHYDE IS A GOOD SUBSTRATE AND NOT AN INHIBITOR OF BETA-LACTAMASE-A AND BETA-LACTAMASE-C

Replacement of the 3-carboxylate residue in phenoxymethylpenicillin by an aldehyde group gives a good substrate for E. cloacae P99 beta-lact amase with k(cat) = 34 s(-1), K-m = 7.5 x 10(-5) mol dm(-3) and k(cat) /K-m = 4.5 x 10(5) dm(3) mol(-1) s(-1) at pH 7. With B. cereus 569/H b eta-lactamase I as a catalyst, k(cat)/K-m = 1.87 x 10(4) dm(3) mol(-1) s(-1) at pH 7 and shows a bell-shaped dependence on pH with apparent pK(a)s of 4.76 and 9.72. Any close proximity between the penicillin 3- aldehyde and a lysine amino group on the protein does not result in im inine formation and inhibition of the enzyme.