Exploring the biosynthetic potential of Korean Actinobacteria for antibacterial metabolite discovery

Actinobacteria, a phylum of Gram-positive bacteria, are renowned for their remarkable ability to produce antibacterial natural products. The National Institute of Biological Resources (NIBR) of Korea maintains a collection of Korean native actinobacteria. In this study, we explored the phylogenetic and biosynthetic diversity of the NIBR actinobacteria collection to assess its potential as a source of new antibacterial natural products. A 16S rDNA-based phylogenetic analysis revealed a high level of genetic diversity within the collection, with a predominance of Streptomyces, along with rare actinobacterial genera such as Kitasatospora and Micromonospora. Additionally, genetic network analysis of biosynthetic gene clusters (BGCs) from 15 sequenced NIBR actinobacterial strains demonstrated extensive BGC diversity, with many clusters identified as cryptic. Screening of culture extracts for antibacterial activity, followed by dereplication of active extracts, suggested the presence of potentially novel antibacterial natural products. Activity-guided isolation and whole-genome sequencing of the active strain KU57 led to the isolation of one new and three known svetamycin congeners along with their BGC. Overall, our findings highlight the NIBR actinobacteria collection as a valuable source for the discovery of new antibacterial natural products.