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Lugdunomycin, an Angucycline‐Derived Molecule with Unprecedented Chemical Architecture
Author(s) -
Wu Changsheng,
van der Heul Helga U.,
Melnik Alexey V.,
Lübben Jens,
Dorrestein Pieter C.,
Minnaard Adriaan J.,
Choi Young Hae,
van Wezel Gilles P.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201814581
Subject(s) - polyketide , propellane , stereochemistry , stereocenter , chemistry , streptomyces , drug discovery , structural motif , ring (chemistry) , computational biology , biology , bicyclic molecule , enantioselective synthesis , biosynthesis , biochemistry , organic chemistry , bacteria , genetics , catalysis , enzyme
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.