Cystobactamids: myxobacterial topoisomerase inhibitors exhibiting potent antibacterial activity.
Angew Chem Int Ed Engl
; 53(52): 14605-9, 2014 Dec 22.
Article
em En
| MEDLINE
| ID: mdl-25510965
ABSTRACT
The development of new antibiotics faces a severe crisis interâ
alia owing to a lack of innovative chemical scaffolds with activities against Gram-negative and multiresistant pathogens. Herein, we report highly potent novel antibacterial compounds, the myxobacteria-derived cystobactamids 1-3, which were isolated from Cystobacter sp. and show minimum inhibitory concentrations in the low µg mL(-1) range. We describe the isolation and structure elucidation of three congeners as well as the identification and annotation of their biosynthetic gene cluster. By studying the self-resistance mechanism in the natural producer organism, the molecular targets were identified as bacterial typeâ
IIa topoisomerases. As quinolones are largely exhausted as a template for new type II topoisomerase inhibitors, the cystobactamids offer exciting alternatives to generate novel antibiotics using medicinal chemistry and biosynthetic engineering.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asparagina
/
Proteínas de Bactérias
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Myxococcales
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DNA Topoisomerases Tipo I
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Inibidores da Topoisomerase
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Antibacterianos
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Nitrocompostos
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article