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β-Lactams from the Ocean

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-...

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Autores principales: Fisher, Jed F., Mobashery, Shahriar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963991/
https://www.ncbi.nlm.nih.gov/pubmed/36827127
http://dx.doi.org/10.3390/md21020086
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author Fisher, Jed F.
Mobashery, Shahriar
author_facet Fisher, Jed F.
Mobashery, Shahriar
author_sort Fisher, Jed F.
collection PubMed
description 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.
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spelling pubmed-99639912023-02-26 β-Lactams from the Ocean Fisher, Jed F. Mobashery, Shahriar Mar Drugs Review 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. MDPI 2023-01-25 /pmc/articles/PMC9963991/ /pubmed/36827127 http://dx.doi.org/10.3390/md21020086 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Fisher, Jed F.
Mobashery, Shahriar
β-Lactams from the Ocean
title β-Lactams from the Ocean
title_full β-Lactams from the Ocean
title_fullStr β-Lactams from the Ocean
title_full_unstemmed β-Lactams from the Ocean
title_short β-Lactams from the Ocean
title_sort β-lactams from the ocean
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963991/
https://www.ncbi.nlm.nih.gov/pubmed/36827127
http://dx.doi.org/10.3390/md21020086
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