Overall, we show a here enhancement in the biomolecular features of an anthropogenic enzyme, from a starting point that had already been heavily optimized through both laboratory evolution (using ancestral protein as scaffolds) and protein engineering. Taken together, our results both provide insight into the molecular mechanisms of enzyme evolution and demonstrate a highly efficient experimental/computational approach to catalysis/stability enhancement that will contribute to expand the scope of biotechnological applications of enzymes through targeted engineering of protein conformational dynamics.