Parallel molecular mechanisms for enzyme temperature adaptation

The mechanisms that underly the adaptation of enzyme activities and stabilities to temperature are fundamental to our understanding of molecular evolution and how enzymes work. Here, we investigate the molecular and evolutionary mechanisms of enzyme temperature adaption, combining deep mechanistic studies with comprehensive sequence analyses of thousands of enzymes. We show that temperature adaptation in ketosteroid isomerase (KSI) arises primarily from one residue change with limited, local epistasis, and we establish the underlying physical mechanisms. This residue change occurs in diverse KSI backgrounds, suggesting parallel adaptation to temperature. We identify residues associated with organismal growth temperature across 1005 diverse bacterial enzyme families, suggesting widespread parallel adaptation to temperature. We assess the residue properties, molecular interactions, and interaction networks that appear to underly temperature adaptation.

Automated summary

This study reveals the molecular and evolutionary mechanisms of enzyme temperature adaptation, identifying that temperature adaptation in KSI primarily comes from a single residue change with limited, local epistasis. Residues associated with organismal growth temperature are also found across diverse bacterial enzyme families, suggesting widespread parallel adaptation to temperature. The study assesses residue properties, molecular interactions, and interaction networks that appear to underly temperature adaptation.