A global survey of specialized metabolic diversity encoded in bacterial genomes

Bacterial secondary metabolites have been studied for decades for their usefulness as drugs, such as antibiotics. However, the identification of new structures has been decelerating, while multi-resistant pathogens continue to emerge. It is unclear how much chemical diversity exists in Nature and whether discovery efforts should be focused on established antibiotic producers or rather on understudied taxa. Here, we surveyed around 170,000 bacterial genomes and several thousand of Metagenome Assembled Genomes (MAGs). Our results indicate that only 3% of the genomic potential for natural products has been experimentally discovered. Our analysis connects the emergence of most biosynthetic diversity in evolutionary history close to the taxonomic rank of genus, identifies Streptomyces as by far the most biosynthetically diverse, followed by producers from genera such as Amycolatopsis, Kutzneria and Micromonospora, and highlights multiple promising high-producing taxa that have thus far been less investigated, such as Weeksellaceae (Bacteroidota), Myxococcaceae (Myxococcota), Pleurocapsa, Nostocaceae (Cyanobacteria).