The function and evolution of penicillinase

Abstract In order to construct biologically useful hypotheses on plausible pathways for the evolution of an enzyme, it is important to know something about the probable physiological function, as well as the chemistry, of the molecular varieties existing at present. Yet, function of a part of an organism—be it a morphological entity or simply a species of protein—is a notoriously subjective quality, difficult to assess without intimate knowledge of the life history of the organism and its natural ecological relationships. Chemical structure, for these purposes, is equivalent to amino acid sequence, for it is by comparison of different sequences in a homologous series of proteins that some idea can be obtained as to the most likely steps in their biochemical evolution at the level of the structural genes concerned. In this critical review, it is argued that existing evidence on the whole tends to favour the conclusion that the β-lactamases function in general as detoxifying agents, acting against the penicillins and cephalosporins, and that their evolutionary history has been tuned by selection in a natural environment where these classes of compound have operated as specific inhibitors of bacterial growth.