Lugdunomycin,an Angucycline‐Derived Molecule with Unprecedented Chemical Architecture |
| |
Authors: | Changsheng Wu Helga U vanderHeul Alexey V Melnik Jens Lübben Pieter C Dorrestein Adriaan J Minnaard Young Hae Choi Gilles P vanWezel |
| |
Institution: | Changsheng Wu,Helga U. van der Heul,Alexey V. Melnik,Jens Lübben,Pieter C. Dorrestein,Adriaan J. Minnaard,Young Hae Choi,Gilles P. van Wezel |
| |
Abstract: | 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. |
| |
Keywords: | angucycline Baeyer– Villiger oxidation molecular networking natural product polyketide |
|
|