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

Natalia M Vior,Rodney Lacret,Alicia H Russell,Andrew W Truman,Edward S Hems

doi:10.1039/d1sc01456k

Natalia M Vior, Rodney Lacret + Show 3 more

Open Access

https://doi.org/10.1039/d1sc01456k

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Journal: Chemical science	Publication Date: Jan 1, 2021
Citations: 9	License type: CC BY 3.0

Affiliation: John Innes Centre

Abstract

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.

Highlights

Microorganisms produce an array of natural products (NPs) with diverse and important biological activities.[1]
The most abundant peptide family (“Network 1”) consisted of 231 peptides whose Ribosomally synthesised and post-translationally modi ed peptides (RiPPs) products were completely unknown and only 78 were originally annotated as genes. To determine whether this precursor peptide family was present in other phyla, further analyses using BLAST34 and RiPPER were carried out
This study shows that the application of targeted genome mining tools is a valuable approach to identify uncharacterised novel biosynthetic gene clusters

Summary

Introduction

Microorganisms produce an array of natural products (NPs) with diverse and important biological activities.[1]. The sequence variation of both the identi ed precursor peptides, as well as the associated RTEs, suggests that these BGCs produce structurally distinct molecules with variable post-translational modi cations.

Results

Conclusion