Lugdunomycin, an Angucycline-Derived Molecule with Unprecedented Chemical Architecture

Changsheng Wu, Helga U. van der Heul, Alexey V. Melnik, Jens Luebben, Pieter C. Dorrestein, Adriaan J. Minnaard, Young Hae Choi, Gilles P. van Wezel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)2809-2814
Number of pages6
JournalAngewandte Chemie-International Edition
Volume58
Issue number9
DOIs
Publication statusPublished - 25-Feb-2019

Keywords

  • angucycline
  • Baeyer-Villiger oxidation
  • molecular networking
  • natural product
  • polyketide
  • NATURAL-PRODUCTS
  • ANTIBIOTICS
  • BIOSYNTHESIS
  • EXPLORE

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