Why Do Filamentous Actinomycetota Produce Such a Vast Array of Specialized Metabolites?

Bacteria of the phylum Actinomycetota are extremely diverse: They inhabit niches ranging from soils and ocean sediments to the normal human microbiota, and they cause tuberculosis, one of the most prevalent chronic bacterial infections. They display an accordingly wide range of adaptive traits that enable their persistence, including, in some clades, a vast repertoire of biologically active small molecules. While humans have capitalized on this trove of useful natural products (also called secondary or specialized metabolites), the utility of these molecules for their producers has been challenging to directly assess. In this review, we consider adaptations that may have paved the way for the evolution of the expansive specialized metabolisms present in certain clades of Actinomycetota. We also consider the evolutionary pressures that may have driven diversification of these metabolisms and document how these organisms use these molecules in microbial interactions.