The Myxobacterial Genus Archangium: A Prolific and Underexploited Source of Bioactive Secondary Metabolites

Abstract

The genus Archangium, a cryptic group of myxobacteria, is a rich source of diverse secondary metabolites. This study reviews the chemical structures and discovery history of 55 secondary metabolites, analyzing the relationship between the chemical structures of these compounds and their bioactivity profiles through molecular networking. Notably, 63.6% of the compounds exhibit potent antimicrobial (MIC < 1 μg/mL) and/or cytotoxic activities (IC₅₀ < 1 μg/mL). Advances in the biosynthetic gene clusters and biosynthetic pathways of seven classes of identified compounds are also presented. Finally, genomic mining approaches are applied to analyze the potential for Archangium strains to synthesize analogs of identified bioactive natural products, uncovering that 98.7% of their secondary metabolic potential remains unexplored. This study highlights the vast potential of Archangium bacteria in synthesizing clade-specific novel secondary metabolites, particularly ribosomally synthesized and post-translationally modified peptide natural products, offering valuable insights for the targeted discovery and biosynthesis of new natural products from this genus.