Genome Mining of Streptomyces sp. PB17 from Cuatro Ciénegas Basin Reveals Biosynthetic Potential for Novel Neurotherapeutics

The Cuatro Ciénegas Basin (CCB), a biodiversity hotspot in Coahuila, Mexico, harbors microbial communities adapted to extreme oligotrophic conditions, making it a promising site for novel bioactive compound discovery.. This study reports the isolation, whole-genome sequencing, and analysis of Streptomyces sp. PB17, a thermotolerant actinomycete retrieved from the karstic Poza La Becerra. Phylogenomic analyses including TYGS and VBCG pipelines, combined with ANI values, support its classification as a putatively novel species. Streptomyces PB17’s genome mining revealed 31 biosynthetic gene clusters (BGCs), with over 10 exhibiting low similarity to known pathways, highlighting its potential for novel bioactive compounds. Among these, ribosomally synthesized and post-translationally modified peptides (RiPPs) demonstrated strong predictive scores for blood-brain barrier penetration properties, representing promising candidates for neurotherapeutic applications. These findings underscore the biotechnological potential of actinomycetes retrieved from extreme sites and emphasize the importance of underexplored ecosystems like the CCB in natural product discovery, including neurotherapeutic research.