Exploring New Avenues for Lanthipeptide Engineering

The rise of antibiotic resistance and emerging viral diseases threatens global health. This research explores a special group of natural products called lanthipeptides—ribosomally synthesized and post-translationally modified peptides with unique structures that make them biologically active. These peptides hold great potential as future antibiotics and antiviral drugs. The study begins by identifying and producing a new lanthipeptide, estercin A, using engineered bacteria. Estercin A showed strong activity against serious pathogens, including antibiotic-resistant strains, while also remaining stable under various conditions. Next, we altered the structure of another lanthipeptide, nisin, by introducing at one residue position different amino acids. These modifications changed their antimicrobial specificity. Furthermore, parts of the nisin molecule were replaced or fused to different amino acid sequences and coupled to lipid chains to test the impact on the antimicrobial activity. One lipid modification in particular, caused significantly increased activity. Finally, the research explored the use of lanthionine-synthesis based strategies against viruses by designing cyclic peptides that affect the activity of HIV integrase. Some of these engineered molecules showed promising antiviral activity. Taken together, this work demonstrates that by reprogramming natural molecules, we can design next-generation antimicrobial and anti-viral agents. The approach opens new directions for combating drug-resistant infections and developing targeted peptide-based medicines.