Naturally Occurring β-Lactams

Southgate, Robert; Elson, Stephen W.

doi:10.1007/978-3-7091-8790-6_1

Cited by 13 publications

(7 citation statements)

References 280 publications

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“…An important class of NPs in the fight against antibiotic resistance is that of resistance inhibitors. Penicillins are still the most administered antibiotics [ 29 , 107 ], but resistance caused by β-lactamases was discovered almost as soon as the antibiotic itself [ 1 ] and has become a major problem for their clinical application [ 126 ]. The combined use of β-lactam antibiotics together with β-lactamase inhibitors is exemplified by the combination of amoxicillin and clavulanic acid, marketed as Augmentin ® [ 31 , 35 ].…”

Section: Experimental Approaches Based On Nmr Metabolomicsmentioning

confidence: 99%

Metabolic profiling as a tool for prioritizing antimicrobial compounds

Choi

Wezel

2016

Journal of Industrial Microbiology and Biotechnology

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Metabolomics is an analytical technique that allows scientists to globally profile low molecular weight metabolites between samples in a medium- or high-throughput environment. Different biological samples are statistically analyzed and correlated to a bioactivity of interest, highlighting differentially produced compounds as potential biomarkers. Here, we review NMR- and MS-based metabolomics as technologies to facilitate the identification of novel antimicrobial natural products from microbial sources. Approaches to elicit the production of poorly expressed (cryptic) molecules are thereby a key to allow statistical analysis of samples to identify bioactive markers, while connection of compounds to their biosynthetic gene cluster is a determining step in elucidating the biosynthetic pathway and allows downstream process optimization and upscaling. The review focuses on approaches built around NMR-based metabolomics, which enables efficient dereplication and guided fractionation of (antimicrobial) compounds.

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Section: Experimental Approaches Based On Nmr Metabolomicsmentioning

confidence: 99%

Metabolic profiling as a tool for prioritizing antimicrobial compounds

Choi

Wezel

2016

Journal of Industrial Microbiology and Biotechnology

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“…1) and represented by the olivanic acids and thienamycins [1,2]. Their structures differ from the classical b-lactam antibiotics in that they harbor a highly strained 4,5-bicyclic ring system based on an unsaturated five-membered ring in which a methylene replaces the sulfur atom in position 1 and the C-6 acylamino-substituent of the bicyclic b-lactam ring is replaced by a carbon substituent, which is invariably an ahydroxyethyl group [3].…”

Section: Historical Overviewmentioning

confidence: 99%

“…During that time, researchers at Merck managed to isolate the thienamycin family of carbapenems from S. cattleya [2]. Since then, a broad series of carbapenem analogues, e.g., carpetimycin A and asparenomycin A, have been isolated from Streptomyces spp.…”

Section: Historical Overviewmentioning

confidence: 99%

“…Among the first b-lactamase inhibitors discovered were the olivanic acids, so called because they were isolated from a strain of Streptomyces olivaceus [4]. These new compounds were not only b-lactamase inhibitors but showed potent antibacterial activity.During that time, researchers at Merck managed to isolate the thienamycin family of carbapenems from S. cattleya [2]. Since then, a broad series of carbapenem analogues, e.g., carpetimycin A and asparenomycin A, have been isolated from Streptomyces spp.…”

mentioning

confidence: 99%

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Cellular and molecular aspects of drugs of the future: meropenem

Cottagnoud¹

2002

CMLS, Cell. Mol. Life Sci.

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Meropenem, first synthesized in the late eighties, has become one of the most important beta-lactam antibiotics of the carbapenem subclass used for the treatment of a variety of life-threatening infections. Due to its unique chemical structure, meropenem is not inactivated by the kidney dehydropeptidase I and the majority of microbial beta-lactamases. Its antimicrobial activity is based on its high affinity for the majority of cell wall-synthesizing enzymes, the so-called penicillin-binding proteins, of Gram-positive and -negative bacteria. However, bacteria have evolved several approaches to resist meropenem: (i) by reducing the affinity of the penicillin-binding proteins for the antibiotics, (ii) by decreasing the permeability of the outer membrane of Gram-negative bacteria, (iii) by using efflux pumps, and (iv) by activating zinc-dependent carbapenemases. Meropenem has a low toxicity profile and, in contrast to imipenem, no central nervous system toxicity.

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“…ß-Lactamase inhibitors are a clinically important class of compounds capable of protecting ß-lactam antibiotics from inactivation by bacterial ßlactamases. Screening for inhibitors of this type has been carried out extensively in Actinomycetes, and has resulted in the discovery of clavulanic acid (1) and numerous carbapenem antibiotics (2). However, only rarely were inhibitors of a nonß-lactam structure (3)(4)(5)(6) isolated from this group of organisms.…”

mentioning

confidence: 99%