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

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.