ABSTRACT
Korea, being surrounded by the sea, provides a rich habitat for marine sponges, which have been a prolific source of bioactive natural products. Although a diverse array of structurally novel natural products has been isolated from Korean marine sponges, their biosynthetic origins remain largely unknown. To explore the biosynthetic potential of Korean marine sponges, we conducted metagenomic analyses of sponges inhabiting the East Sea of Korea. This analysis revealed a symbiotic association of
Candidatus
Entotheonella bacteria with Halichondria sponges. Here, we report a new chemically rich Entotheonella variant, which we named
Ca
. Entotheonella halido. Remarkably, this symbiont makes up 69% of the microbial community in the sponge
Halichondira dokdoensis
. Genome-resolved metagenomics enabled us to obtain a high-quality
Ca
. E. halido genome, which represents the largest (12 Mb) and highest quality among previously reported
Entotheonella
genomes. We also identified the biosynthetic gene cluster (BGC) of the known sponge-derived Halicylindramides from the
Ca
. E. halido genome, enabling us to determine their biosynthetic origin. This new symbiotic association expands the host diversity and biosynthetic potential of metabolically talented bacterial genus
Ca
. Entotheonella symbionts.
IMPORTANCE
Our study reports the discovery of a new bacterial symbiont
Ca
. Entotheonella halido associated with the Korean marine sponge
Halichondria dokdoensis
. Using genome-resolved metagenomics, we recovered a high-quality
Ca
. E. halido MAG (Metagenome-Assembled Genome), which represents the largest and most complete
Ca
. Entotheonella MAG reported to date. Pangenome and BGC network analyses revealed a remarkably high BGC diversity within the
Ca
. Entotheonella pangenome, with almost no overlapping BGCs between different MAGs. The cryptic and genetically unique BGCs present in the
Ca
. Entotheonella pangenome represents a promising source of new bioactive natural products.