• The phylogenetic distribution of GT1 family enzymes showed domain-dependent pattern. • The domain-dependent characterized GTs showed distinct substrates spectrum. • Two regions that discriminate the GT1 enzymes from different domains were identified.

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.

This review presents a comprehensive overview of recent advances in the discovery methodologies, new structures, bioactivities, and unique biosynthetic logics of myxobacterial natural products reported from January 2017 to November 2023.