Advances in lasso peptide discovery, biosynthesis, and function

Lasso peptides are a large and sequence-diverse class of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products characterized by their slip knot-like shape. These unique, highly stable peptides are produced by bacteria for various purposes. Their stability and sequence diversity make them a potentially useful scaffold for biomedically relevant folded peptides. However, many questions remain about lasso peptide biosynthesis, ecological function, and diversification potential for biomedical and agricultural applications. This review discusses new insights and open questions about lasso peptide biosynthesis and biological function. The role that genome mining has played in the development of new methodologies for discovering and diversifying lasso peptides is also discussed.