β-Lactams from the Ocean

The title of this essay is as much a question as it is a statement. The discovery of the beta-lactam antibiotics-including penicillins, cephalosporins, and carbapenems-as largely (if not exclusively) secondary metabolites of terrestrial fungi and bacteria, transformed modern medicine. The antibiotic beta-lactams inactivate essential enzymes of bacterial cell-wall biosynthesis. Moreover, the ability of the beta-lactams to function as enzyme inhibitors is of such great medical value, that inhibitors of the enzymes which degrade hydrolytically the beta-lactams, the beta-lactamases, have equal value. Given this privileged status for the beta-lactam ring, it is therefore a disappointment that the exemplification of this ring in marine secondary metabolites is sparse. It may be that biologically active marine beta-lactams are there, and simply have yet to be encountered. In this report, we posit a second explanation: that the value of the beta-lactam to secure an ecological advantage in the marine environment might be compromised by its close structural similarity to the beta-lactones of quorum sensing. The steric and reactivity similarities between the beta-lactams and the beta-lactones represent an outside-of-the-box opportunity for correlating new structures and new enzyme targets for the discovery of compelling biological activities.

Automated summary

This essay discusses the discovery of beta-lactam antibiotics and their transformation of modern medicine, while also pointing out the scarcity of beta-lactam compounds in marine organisms and their potential similarity to quorum sensing molecules. The author proposes the exploration of this similarity to discover new structures and enzyme targets for interesting biological activities.