Systematic investigation of the link between enzyme catalysis and cold adaptation

Cold temperature is prevalent across the biosphere and slows the rates of chemical reactions. Increased catalysis has been predicted to be a general adaptive trait of enzymes to reduced temperature, and this expectation has informed physical models for enzyme catalysis and influenced bioprospecting strategies. To broadly test rate as an adaptive trait to cold, we paired kinetic constants of 2223 enzyme reactions with their organism’s optimal growth temperature (T_Growth) and analyzed trends of rate as a function of T_Growth. These data do not support a prevalent increase in rate in cold adaptation. In the model enzyme ketosteroid isomerase (KSI), there was prior evidence for temperature adaptation from a change in an active site residue that results in a tradeoff between activity and stability. Here, we found that little of the overall rate variation for 20 KSI variants was accounted for by T_Growth. In contrast, and consistent with prior expectations, we observed a correlation between stability and T_Growth across 433 proteins. These results suggest that temperature exerts a weaker selection pressure on enzyme rate than stability and that evolutionary forces other than temperature are responsible for the majority of enzymatic rate variation.