The Role of Epistatic Interactions in the Evolution of New Enzyme Functions in the Enolase Superfamily

Abstract

The factors that enable enzymes to evolve new functions and specificities are not well understood. Two factors that influence enzyme evolution are enzyme promiscuity and epistasis. Enzymes are said to be promiscuous if their active site has the ability to catalyze more than one reaction. Epistasis occurs when amino acid substitutions have different effects when placed in different sequence contexts. Understanding the role that factors like enzyme promiscuity and epistasis play in the evolution of new enzyme functions will enable scientists to design enzymes with new functions. Here, I seek to understand how promiscuity and epistasis have influenced the evolution of enzymes within the enolase superfamily. I examine the differing roles that the conserved residues G254 and R128 play in two enzymes in the OSBS family, T. fusca and E. coli OSBS. I also examine the role that a conserved second shell amino acid, R266, played in the evolution of racemase and epimerase activities in the enolase superfamily.