Endolysins are enzymes that degrade the bacterial cell wall, resulting in a quick cell death. They are

recognized as a novel class of antibiotics with high potential. A unique feature that differentiates

them from all know antibiotic classes is their modular nature, comprising two to four modules with

a dedicated function. Swapping of these modules yields antibiotics with desired and improved

properties in a process that we call the synthetic biology of modular proteins. We have developed a

technique –VersaTile Shuffling –which excels in the convenience, efficiency and throughput of

module shuffling and we can now produce millions of modular variants per day. With this project

we aim to build microdroplet-based assays using recent advances in microfluidics to study the

structure-activity relationship between the modular composition and antibacterial properties of this

novel class of antibiotics, and to select the best modular endolysin variants out of millions of

variants. Such ultra-high-throughput selection technology for protein engineering will deliver

candidate endolysins for a personalized medicine of infectious diseases, or to prevent or treat

rapidly emerging bacterial epidemics in agriculture and food industry. In extension, the combination

of VersaTile Shuffling and microdroplet-based assays for protein engineering will spur similar

research projects with modular proteins in our research group in the field of protein engineering.