Prediction, production and characterization of post-translationally modified antimicrobial peptides

Pathogenic bacteria are rapidly becoming resistant to the currently used antibiotics therefore we need novel antibiotics, preferably with new mechanisms of action. One potential source are the so called antimicrobial peptides that are produced by many different organisms. To gain access to these potential drugs, software (BAGEL3) was developed to assess the potential of bacteria to produce these compounds based on their genome. As more and more genomes sequences are defined this software can help to focus screening efforts based on (meta)-genomes. Predictions made by this software were subsequently used to produce novel antimicrobial peptides demonstrating the correctness of the predictions. Additionally these predictions were used in a synthetic biology approach to produce and modify so called lantibiotics from synthesized DNA. This approach is independent of the source organism and thus enables the production of antibiotics from unculturable bacteria. Finally this resulted in six new lead-compounds with antimicrobial activity against clinically relevant pathogens