(462g) Engineering Ribosomal Natural Products As New Antimicrobials

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an emerging class of natural products. The precursors to RiPPs are linear polypeptides assembled at the ribosome which are subsequently tailored by the action of multiple enzymes into the final natural product. One subclass of RiPPs are the lasso peptides, several of which have promising antimicrobial activities. In this talk I will focus on the discovery, activity, and engineering of the antimicrobial lasso peptide ubonodin. This peptide, encoded in some Burkholderia ubonensis genomes, was originally of interest because of its large size (28 aa) relative to other lasso peptides. Serendipitously, ubonodin was also found to have activity against multiple members of the Burkholderia cepacia complex, a group of related bacteria that cause disease, especially in those afflicted with cystic fibrosis.