Abstract
Bacterial specialized metabolites are a proven source of antibiotics and cancer therapies, but whether we have sampled all the secondary metabolite chemical diversity of cultivated bacteria is not known. We analysed ~ 170,000 bacterial genomes and ~ 47,000 metagenome assembled genomes (MAGs) using a modified BiG-SLiCE and the new clust-o-matic algorithm. We found that only 3% of the natural products potentially encoded in bacterial genomes have been experimentally characterized. We show that the variation of secondary metabolite biosynthetic diversity drops significantly at the genus level, identifying it as an appropriate taxonomic rank for comparison. Equal comparison of genera based on Relative Evolutionary Distance revealed that Streptomyces bacteria encode the largest biosynthetic diversity by far, with Amycolatopsis, Kutzneria and Micromonospora also encoding substantial diversity. Finally we find that several less-well-studied taxa, such as Weeksellaceae (Bacteroidota), Myxococcaceae (Myxococcota), Pleurocapsa and Nostocaceae (Cyanobacteria), have potential to produce highly diverse sets of secondary metabolites that warrant further investigation.
Competing Interest Statement
M.H.M. is a co-founder of Design Pharmaceuticals and a member of the scientific advisory board of Hexagon Bio. The other authors declare no competing interests.
Footnotes
↵** These authors jointly supervised this work: Marnix H. Medema, Nadine Ziemert.
↵+ e-mail: marnix.medema{at}wur.nl
Small changes have been made in various locations to improve readability and provide additional explanation where needed. The list of references has been reduced. The DOI of the zenodo repository has been updated to the latest version.