# Co-option of an ancestral peptidase controls developmental patterning in multicellular cyanobacteria

## TL;DR

A study shows how an ancient enzyme in cyanobacteria evolved to control cell patterning, similar to processes in more complex organisms.

## Contribution

The study reveals that an ancestral peptidase was co-opted to process a peptide, enabling spatial patterning in cyanobacteria.

## Key findings

- PatX is exported and cleaved by PatP to produce HRGTGR, which inhibits HetR.
- PatP predates PatX and HetR, suggesting it was repurposed for patterning.
- The PatP-PatX-HetR module evolved in filamentous cyanobacteria.

## 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.

•PatX is exported to the periplasm and cleaved by PatP•PatX-derived HRGTGR peptide binds and inactivates HetR, blocking heterocyst differentiation•Ancestral cyanobacterial peptidase PatP predates both PatX and HetR•The PatP-PatX-HetR module evolved in filamentous cyanobacteria

PatX is exported to the periplasm and cleaved by PatP

PatX-derived HRGTGR peptide binds and inactivates HetR, blocking heterocyst differentiation

Ancestral cyanobacterial peptidase PatP predates both PatX and HetR

The PatP-PatX-HetR module evolved in filamentous cyanobacteria

Developmental biology