Synthetic fusion protein design and applications

Abstract

Synthetic fusion proteins can be designed to achieve improved properties or new functionality by synergistically incorporating multiple proteins into one complex. The fusion of two or more protein domains enhances bioactivities or generates novel functional combinations with a wide range of biotechnological and (bio)pharmaceutical applications. In this review, initially, we summarize the commonly used approaches for constructing fusion proteins. For each approach, the design strategy and desired properties are elaborated with examples of recent studies in the areas of biocatalysts, protein switches and bio-therapeutics. Subsequently, the progress in structural prediction of fusion proteins is presented, which can potentially facilitate the structure-based systematic design of fusion proteins toward identifying the best combinations of fusion partners. Finally, the current challenges and future directions in this field are discussed.

Keywords: Domain insertion; Fusion protein; Linker design; Protein therapeutics; Synthetic protein engineering.