Evolution and Thermoadaptation in Enzymes

How have enzymes evolved since life appeared on Earth? What has driven the adaptation of enzyme catalysis to different temperatures? Although massive work has been done, in 2017 these are still “hot” questions searching for answers. An interesting paper by Nguyen et al., just appeared on Science, tackled this unsolved issue by investigating the molecular mechanisms underlying thermoadaptation of enzyme catalysis through ancestral sequence reconstruction spanning 3 billion years of evolution, and using as a study-case the adenylate kinase (Adk). The authors assumed as true the well-supported hot-start hypothesis, which implies that life adapted to cooler temperatures because of the Earth’s cooling. According to this, a thermophilic enzyme had to adapt to maintain a high catalytic activity even at lower temperatures, while accommodating relaxed selection on thermostability. It has been hypothesized that enzymes overcame this thermal kinetic hurdle by reducing the enthalpic activation barrier. However, Nguyen et al., by reconstructing eight nodes of the Adk lineage and expressing them together with four modern Adk enzymes, found out something different. Indeed, from the analysis of the Eyring plots, they showed that the oldest ancestors had a strongly negative change in heat capacity of activation, which can explain their extreme slow catalysis at low temperatures. Conversely, along the thermoadaptation process toward cooler temperatures, this kinetic obstacle has been progressively removed, bringing the heat capacity of activation to zero. This close to zero heat capacity of activation was also observed for thermophilic enzymes evolved from mesophilic ancestors, but not for modern hyperthermophiles that remained thermophilic throughout their evolutionary pathway. This represents also a prove of the "evolutionary memory" of enzymes. To find out more about this new scenario, see here for the full manuscript.