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Cystobactamids: myxobacterial topoisomerase inhibitors exhibiting potent antibacterial activity.

Authors
Type
Published Article
Journal
Angewandte Chemie International Edition in English
1521-3773
Publisher
Wiley Blackwell (John Wiley & Sons)
Publication Date
Volume
53
Issue
52
Pages
14605–14609
Identifiers
DOI: 10.1002/anie.201409964
PMID: 25510965
Source
Medline
Keywords
License
Unknown

Abstract

The development of new antibiotics faces a severe crisis inter 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 type 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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