Penicillin 3-aldehyde is a good substrate and not an inhibitor of β-lactamases A and C

Abstract

Replacement of the 3-carboxylate residue in phenoxymethylpenicillin by an aldehyde group gives a good substrate for E. cloacae P99 β-lactamase with k_cat= 34 s^–1, K_m= 7.5 × 10^–5 mol dm^–3 and k_cat/K_m= 4.5 × 10⁵ dm³ mol^–1 s^–1 at pH 7. With B. cereus 569/H β-lactamase I as a catalyst, k_cat/K_m= 1.87 × 10⁴ dm³ mol^–1 s^–1 at pH 7 and shows a bell-shaped dependence on pH with apparent pK_as 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 iminine formation and inhibition of the enzyme.