Parallel molecular mechanisms for enzyme temperature adaptation

The mechanisms that underly the adaptation enzyme activities and
stabilities to temperature are fundamental to our understanding of
molecular evolution and how enzymes work. Herein, 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 in 1005 diverse bacterial enzyme families, suggesting
widespread parallel adaptation. We assess the properties of these
residues, molecular interactions and interaction networks that appear to
underly temperature adaptation.