Discovery and characterisation of an amidine-containing ribosomally-synthesised peptide that is widely distributed in nature

Autor: Andrew W. Truman, Natalia M. Vior, Edward S. Hems, Rodney Lacret, Alicia H Russell
Rok vydání: 2021
Předmět:
Zdroj: Chemical Science
ISSN: 2041-6520
Popis: Ribosomally synthesised and post-translationally modified peptides (RiPPs) are a structurally diverse class of natural product with a wide range of bioactivities. Genome mining for RiPP biosynthetic gene clusters (BGCs) is often hampered by poor annotation of the short precursor peptides that are ultimately modified into the final molecule. Here, we utilise a previously described genome mining tool, RiPPER, to identify novel RiPP precursor peptides near YcaO-domain proteins, enzymes that catalyse various RiPP post-translational modifications including heterocyclisation and thioamidation. Using this dataset, we identified a novel and diverse family of RiPP BGCs spanning over 230 species of Actinobacteria and Firmicutes. A representative BGC from Streptomyces albidoflavus J1074 (formerly known as Streptomyces albus) was characterised, leading to the discovery of streptamidine, a novel amidine-containing RiPP. This new BGC family highlights the breadth of unexplored natural products with structurally rare features, even in model organisms.
Genome mining for pathways containing YcaO proteins revealed a widespread novel family of RiPP gene clusters. A model gene cluster was characterised through genetic and chemical analyses, which yielded streptamidine, a novel amidine-containing RiPP.
Databáze: OpenAIRE