Jiménez, Diego JavierMarasco, RamonaSchultz, JúniaRodríguez, Carlos Andrés DíazNogales, JuanRodriguez-R, Luis MiguelOvermann, JörgRosado, Alexandre Soares2026-03-032026-03-032026-01-30Jiménez, D. J., Marasco, R., Schultz, J., & Rodríguez, C. A. D. et al. (2026). Discovery and cultivation of prokaryotic taxa in the age of metagenomics and artificial intelligence. ISME Journal, 20(1), Article wrag012. https://doi.org/10.1093/ismejo/wrag0121751-736283c647b4-6f01-4cb3-a377-88842c1ca5c4http://hdl.handle.net/10400.14/57235Despite advances in sequencing, microbial genomics, and cultivation techniques, the vast majority of prokaryotic species remain uncultured, which is a persistent bottleneck in microbiology and microbial ecology. This perspective outlines a conceptual framework to improve the transition from genomeresolved metagenomics to the targeted isolation of yet-uncultured prokaryotic taxa. The proposed framework integrates the induced reshaping of microbiomes, genome-based inferences of physiological and phenotypic traits, culture media design, and targeted culturomics, enabling hypothesis-driven cultivation. In addition, this manuscript addresses the critical limitations in the field, including the sequence-to-function gap, and emphasizes the synergistic potential of experimental microbiology, microbial ecology, metagenomics, and artificial intelligence (AI)-based predictions to enhance rational and actionable roadmaps for discovering and cultivating novel prokaryotic lineages.engCulturomicsGenome-scale metabolic modelsGenotype-phenotype inferenceIsolationMachine learningMetagenome-assembled genomesMicrobiome perturbationresearch article10.1093/ismejo/wrag01210503097997141615027001698333100001