Ripp

RiPP stands for ribosomally synthesized and post-translationally modified peptides. This broad class comprises natural products produced by ribosomes as precursor peptides that are then extensively enzymatically modified to yield diverse, often highly modified mature peptides. RiPPs typically exhibit high biological activity, including antimicrobial, antiviral, or enzyme-inhibitory effects, and many have novel structures not seen in non-RiPP natural products.

Biosynthesis and maturation of RiPPs involve a common theme. A precursor peptide is synthesized on the ribosome and contains an N-terminal leader sequence that directs specific post-translational modifications while the C-terminal core is preserved for final activity. The leader is usually removed by a dedicated protease after modifications. A common feature across RiPPs is the clustering of modification enzymes with the precursor gene, forming a RiPP biosynthetic gene cluster. Modifications can include dehydration of serine or threonine residues to dehydro amino acids, formation of crosslinks such as lanthionine or methyllanthionine, heterocyclization of cysteines, and other scaffold-forming transformations. These enzymatic steps generate macrocycles, crosslinks, and unusual side chains that define RiPP diversity and function.

RiPPs encompass several subgroups, such as lantipeptides (lanthipeptides), thiopeptides, sactipeptides, lasso peptides, and cyanobactins. Notable examples include nisin, a lantibiotic used as a food preservative, and thiostrepton, a thiopeptide antibiotic. The RiPP field has grown rapidly, with ongoing efforts to discover new families, elucidate their biosynthetic logic, and engineer gene clusters to produce novel compounds with potential pharmaceutical applications.