# Discovery and cultivation of prokaryotic taxa in the age of metagenomics and artificial intelligence

## TL;DR

This paper proposes a new framework combining metagenomics and AI to help cultivate previously uncultured prokaryotic species, addressing a major challenge in microbiology.

## Contribution

A novel conceptual framework integrating metagenomics, AI, and culturomics for targeted cultivation of uncultured prokaryotes.

## Key findings

- Integrating microbiome reshaping and genome-based traits can guide targeted cultivation.
- The sequence-to-function gap remains a major challenge in prokaryotic cultivation.
- AI-based predictions can enhance rational roadmaps for discovering new prokaryotic lineages.

## Abstract

Despite 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 genome-resolved 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–based predictions to enhance rational and actionable roadmaps for discovering and cultivating novel prokaryotic lineages.

Graphical Abstract
BioRender.com was employed to create the figure

BioRender.com was employed to create the figure