Abstract
Spatial patterning in multicellular organisms is commonly explained by Turing-type reaction-diffusion systems, but the maturation of diffusible inhibitors remains poorly understood. In the cyanobacterium Nostoc PCC 7120, nitrogen deprivation triggers a pattern of nitrogen-fixing heterocysts regulated by HetR and inhibitory peptides, including PatX. We uncover the post-translational mechanism controlling PatX maturation, demonstrating its export and subsequent processing by the peptidase PatP. We identify HRGTGR, a PatX-derived hexapeptide, as the direct inhibitor of HetR, linking maturation to suppressed differentiation. Genomic analyses reveal that patP is ancient and conserved across all cyanobacteria, predating the patX-hetR module found only in filamentous clades. We therefore propose that this ancient peptidase was co-opted to process a new ligand, transforming a proteolytic event into a spatial patterning mechanism. This repurposing parallels eukaryotic signaling, underscoring a universal principle in the emergence of multicellular organization and providing a model for how complex patterns evolve from "simple" components.