TY - JOUR
T1 - Cystobactamids : myxobacterial topoisomerase inhibitors exhibiting potent antibacterial activity
AU - Baumann, Sascha
AU - Herrmann, Jennifer
AU - Raju, Ritesh
AU - Steinmetz, Heinrich
AU - Mohr, Kathrin I.
AU - Huttel, Stephan
AU - Harmrolfs, Kirsten
AU - Stadler, Marc
AU - Muller, Rolf
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/1959.7/uws:28458
U2 - 10.1002/anie.201409964
DO - 10.1002/anie.201409964
M3 - Article
SN - 1433-7851
VL - 53
SP - 14605
EP - 14609
JO - Angewandte Chemie (International Edition)
JF - Angewandte Chemie (International Edition)
IS - 52
ER -