Structural, Energetic, and Mechanistic Determinants of Enzyme Evolvability

Specialized metabolic enzymes originated from primary metabolism, yet their catalytic properties differ significantly from their counterparts in primary metabolism. Whereas primary metabolic enzymes are highly specific and exhibit low levels of mechanistic elasticity, specialized metabolic enzymes, on average, display greater catalytic promiscuity and evolvability. Comparative study of structurally related primary and specialized metabolic enzyme families offers unique opportunities to unveil determining factors of enzyme evolvability. Combining bioinformatics, structural biology, synthetic biology, and biochemistry, we aim to decipher networks consist of energetically coupled residues across a protein fold, which dictate important parameters regarding enzyme evolution, such as protein folding stability and catalytic properties.