Ringing the changes: how bacterial enzymes convert ribosomally-synthesised peptides into antibiotics

Rapid spreading of resistance to commonly used antibiotics is a major healthcare problem. Scientists are constantly searching for new antibiotics, but they are increasingly difficult to find using current knowhow. My study focusses on bacterial enzymes, called YcaOs, which can convert peptides into antibiotics, for example, by introducing various shaped rings into peptides. I will look closely at how YcaOs function by determining their 3D structures. In parallel, I will dig into the huge variety of YcaO-modified peptides predicted to be made by bacteria associated with humans or plants. Finally, I will produce artificial nature-inspired antibiotics using already characterised YcaO enzymes. Cells producing such peptides will be embedded into miniature agar (jelly-like) beads which will serve as tiny Petri dishes. With this system, it is possible to screen millions of peptides over a single day to find new antibiotics, ensuring that the future drug pipeline does not run dry.