Rational Engineering of Enzymes for Enhanced Cold Activity

Temperature-dependent evolution of enzymes allowed for biological adaptation to the wide range of temperatures found across Earth's ecological niches. Adaptation of enzyme activity to low temperatures presents the challenge of providing efficient catalysis with a relative deficiency of thermal energy, while adaptation to high temperatures requires increased thermostability. Evolved and engineered solutions to increasing both hot and cold activity have multiple advantages for industrial applications. Here, we review studies toward engineering important activities for lower temperature catalysis while categorizing three different mechanisms reported to underlie enzymatic cold adaptation: structural flexibility, surface softness, and allosteric dynamics. Further, we analyze the relative efficacy of these mechanisms and conclude that modifying allosteric structural dynamics most frequently leads to the cold temperature adaptation of enzymes. Finally, we offer guidance for rational improvement of low temperature enzymatic activities using allostery pathway mapping tools.