Thermophilic Proteins as Versatile Scaffolds for Protein Engineering

Abstract

Literature from the past two decades has outlined the existence of a trade-off between protein stability and function. This trade-off creates a unique challenge for protein engineers who seek to introduce new functionality to proteins. These engineers must carefully balance the mutation-mediated creation and/or optimization of function with the destabilizing effect of those mutations. Subsequent research has shown that protein stability is positively correlated with "evolvability" or the ability to support mutations which bestow new functionality on the protein. Since the ultimate goal of protein engineering is to create and/or optimize a protein's function, highly stable proteins are preferred as potential scaffolds for protein engineering. This review focuses on the application potential for thermophilic proteins as scaffolds for protein engineering. The relatively high inherent thermostability of these proteins grants them a great deal of mutational robustness, making them promising scaffolds for various protein engineering applications. Comparative studies on the evolvability of thermophilic and mesophilic proteins have strongly supported the argument that thermophilic proteins are more evolvable than mesophilic proteins. These findings indicate that thermophilic proteins may represent the scaffold of choice for protein engineering in the future.

Keywords: evolvability; protein engineering; protein stability; thermophilic proteins.

Figure 1

A schematic of characteristics of thermophilic proteins when compared to mesophilic proteins.

Figure 2

A schematic of facile functional evolution from thermophilic proteins assisted by their high thermostability. Insufficient stability of mesophilic proteins limits their evolvability.