Catalytic diversity and cell wall binding repeats in the phage-encoded endolysins.

Bacteriophage-encoded endolysins can recognize and bind specific bacteria, and act to cleave the glycosidic and/or amide bonds in the peptidoglycan (PG) bacterial cell wall. Cleavage of the cell wall generally results in the death of the bacteria. Their utility as bacteriolytic agents could be exploited for human and veterinary medicines as well as various biotechnological applications. As interest grows in the commercial uses of these proteins, there has been much effort to successfully employ rational design and engineering to produce endolysins with bespoke properties. In this review, we interrogate the current structural data and identify structural features that would be of benefit to engineering the activity and specificity of phage endolysins. We show that the growing body of structural data can be used to predict catalytic residues and mechanism of action from sequences of hypothetical endolysins, and probe the importance of secondary structure repeats in bacterial cell wall-binding domains.