Discovery and engineering of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products

Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent a diverse superfamily of natural products with immense potential for drug development. This review provides a concise overview of the recent advances in the discovery of RiPP natural products, focusing on rational strategies such as bioactivity guided screening, enzyme or precursor-based genome mining, and biosynthetic engineering. The challenges associated with activating silent biosynthetic gene clusters and the development of elaborate catalytic systems are also discussed. The logical frameworks emerging from these research studies offer valuable insights into RiPP biosynthesis and engineering, paving the way for broader pharmaceutic applications of these peptide natural products. The major approaches (i.e. bioactivity-guided screening, genome mining, and biosynthetic engineering) employed in the exploration of RiPP (ribosomally synthesized and post-translationally modified peptides) natural products are discussed in this review.