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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-...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-9963991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT fisherjedf blactamsfromtheocean AT mobasheryshahriar blactamsfromtheocean |