Lugdunomycin, an angucycline‐derived molecule with unprecedented chemical architecture

The angucyclines form the largest family of polycyclic aromatic polyketides, and have been studied extensively. Here we report the discovery of lugdunomycin, a type II polyketide produced by Streptomyces species QL37, which has an unprecedented carbon skeleton synthesized from the angucycline backbone. 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 type II polyketides. Metabolomics combined with MS‐based molecular networking of Streptomyces sp. QL37 identified 24 other rearranged and non‐rearranged angucyclines, whereby 11 of them are previously undescribed. We also propose a biosynthetic route for the limamycins, in addition to that of lugdunomycin. Our work demonstrates that revisiting well‐known compound families and their producer strains still is a promising approach for drug discovery.

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