Cystobactamids : myxobacterial topoisomerase inhibitors exhibiting potent antibacterial activity

Sascha Baumann, Jennifer Herrmann, Ritesh Raju, Heinrich Steinmetz, Kathrin I. Mohr, Stephan Huttel, Kirsten Harmrolfs, Marc Stadler, Rolf Muller

    Research output: Contribution to journalArticlepeer-review

    140 Citations (Scopus)

    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 μmL⁻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.
    Original languageEnglish
    Pages (from-to)14605-14609
    Number of pages5
    JournalAngewandte Chemie (International Edition)
    Volume53
    Issue number52
    DOIs
    Publication statusPublished - 2014

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