The angucyclines form the largest family of polycyclic aromatic polyketides, and have been studied extensively. Herein, we report the discovery of lugdunomycin, an angucycline-derived polyketide, produced by Streptomyces species QL37. Lugdunomycin has unique structural characteristics, including a heptacyclic ring system, a spiroatom, two all-carbon stereocenters, and a benzaza-[4,3,3]propellane motif. Considering the structural novelty, we propose that lugdunomycin represents a novel subclass of aromatic polyketides. Metabolomics, combined with MS-based molecular networking analysis of Streptomyces sp. QL37, elucidated 24 other rearranged and non-rearranged angucyclines, 11 of which were previously undescribed. A biosynthetic route for the lugdunomycin and limamycins is also proposed. This work demonstrates that revisiting well-known compound families and their producer strains still is a promising approach for drug discovery.
CITATION STYLE
Wu, C., van der Heul, H. U., Melnik, A. V., Lübben, J., Dorrestein, P. C., Minnaard, A. J., … van Wezel, G. P. (2019). Lugdunomycin, an Angucycline-Derived Molecule with Unprecedented Chemical Architecture. Angewandte Chemie - International Edition, 58(9), 2809–2814. https://doi.org/10.1002/anie.201814581
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