Rare endophytic actinobacteria from nigeria harbor unique biosynthetic gene clusters with novel antibiotic potential

Actinobacteria are prolific producers of specialized metabolites, including antibiotics; however, much of their biosynthetic potential remains unexplored, particularly within rare genera. This study presents the first genomic insights into the biosynthetic capacity of two rare endophytic actinobacteria, Saccharomonospora xinjiangensis strain PNSac2 and Saccharopolyspora cebuensis strain PGLac3, isolated from medicinal plants in Nigeria. The strains were characterized using morphological analysis, molecular sequencing, phylogenetic inference, average nucleotide identity (ANI), and digital DNA-DNA hybridization (dDDH). Whole-genome sequencing revealed that PNSac2 possesses a 4.7 Mb genome with 45 tRNA genes, 3 rRNA operons, and 4,541 coding sequences (CDSs), while PGLac3 harbors a 6.4 Mb genome comprising 48 tRNA genes, 4 rRNA operons, and 6,372 CDSs. Genome mining using antiSMASH identified 24 biosynthetic gene clusters (BGCs) in PNSac2 and 28 in PGLac3, including clusters encoding polyketides, nonribosomal peptides, siderophores, terpenes, and ribosomally synthesized and post-translationally modified peptides (RiPPs). Many BGCs showed low similarity to known clusters, indicating a strong potential for novel metabolite discovery. Notably, PNSac2 encoded BGCs related to bleomycin, oxalomycin, desertomycin, and ossamycin, while PGLac3 harbored predicted arylpolyene, lanthipeptide, and a unique lassopeptide cluster. Comparative genomics revealed conserved synteny with related species alongside strain-specific BGCs, and phylogenomic analysis confirmed their taxonomic placement. Overall, these findings highlight the untapped biosynthetic diversity of rare Nigerian endophytic actinobacteria and underscore their promise as sources of novel antimicrobial compounds. Targeted genome engineering approaches, including CRISPR-Cas-based strategies, may further enable the activation and exploitation of cryptic biosynthetic pathways in these strains.

The online version contains supplementary material available at 10.1007/s13205-026-04781-4.