New developments in RiPP discovery, enzymology and engineering Montalbán López, Manuel Scott, Thomas A Ramesh, Sangeetha Rahman, Imran R. van Heel, Auke J. Viel, Jakob H. Bandarian, Vahe Dittmann, Elke Genilloud Rodríguez, Olga Goto, Yuki Grande Burgos, María Jose Hill, Colin Seokhee, Kim Koehnke, Jesko Latham, John A. Link, A. James Martínez, Beatriz Nair, Satish K. Nicolet, Yvain Rebuffat, Sylvie Sahl, Hans-Georg Sareen, Dipti Schmidt, Eric W. Schmitt, Lutz Severinov, Konstantin Sussmuth, Roderich D. Truman, Andrew W. Wang, Huan Weng, Jing-Ke van Weze, Gilles P. Zhang, Qi Zhong, Jin Piel, Jorn Mitchell, Douglas A. Kuipers, Oscar P. van der Donk, Wilfred A. Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large group of natural products. A community-driven review in 2013 described the emerging commonalities in the biosynthesis of RiPPs and the opportunities they offered for bioengineering and genome mining. Since then, the field has seen tremendous advances in understanding of the mechanisms by which nature assembles these compounds, in engineering their biosynthetic machinery for a wide range of applications, and in the discovery of entirely new RiPP families using bioinformatic tools developed specifically for this compound class. The First International Conference on RiPPs was held in 2019, and the meeting participants assembled the current review describing new developments since 2013. The review discusses the new classes of RiPPs that have been discovered, the advances in our understanding of the installation of both primary and secondary post-translational modifications, and the mechanisms by which the enzymes recognize the leader peptides in their substrates. In addition, genome mining tools used for RiPP discovery are discussed as well as various strategies for RiPP engineering. An outlook section presents directions for future research. 2026-01-16T10:52:57Z 2026-01-16T10:52:57Z 2021 journal article https://hdl.handle.net/10481/109798 10.1039/d0np00027b eng http://creativecommons.org/licenses/by-nc-nd/4.0/ embargoed access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Royal Society of Chemistry