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- Title
β-Lactams from the Ocean.
- Authors
Fisher, Jed F.; Mobashery, Shahriar
- Abstract
The title of this essay is as much a question as it is a statement. The discovery of the β-lactam antibiotics—including penicillins, cephalosporins, and carbapenems—as largely (if not exclusively) secondary metabolites of terrestrial fungi and bacteria, transformed modern medicine. The antibiotic β-lactams inactivate essential enzymes of bacterial cell-wall biosynthesis. Moreover, the ability of the β-lactams to function as enzyme inhibitors is of such great medical value, that inhibitors of the enzymes which degrade hydrolytically the β-lactams, the β-lactamases, have equal value. Given this privileged status for the β-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 β-lactams are there, and simply have yet to be encountered. In this report, we posit a second explanation: that the value of the β-lactam to secure an ecological advantage in the marine environment might be compromised by its close structural similarity to the β-lactones of quorum sensing. The steric and reactivity similarities between the β-lactams and the β-lactones represent an outside-of-the-box opportunity for correlating new structures and new enzyme targets for the discovery of compelling biological activities.
- Subjects
ACYL-homoserine lactones; BETA lactam antibiotics; METABOLITES; BACTERIAL enzymes; QUORUM sensing; ENZYME inhibitors; OCEAN
- Publication
Marine Drugs, 2023, Vol 21, Issue 2, p86
- ISSN
1660-3397
- Publication type
Article
- DOI
10.3390/md21020086