Integrating genomics and metabolomics for scalable non-ribosomal peptide discovery
| Autor: | Julia Oh, Yan-Ni Shi, Pavel A. Pevzner, Hosein Mohimani, Helge B. Bode, Florian Grundmann, Alexey Gurevich, Changhui Guan, Morgan Panitchpakdi, Amina Bouslimani, Edna Bode, Andrés Mauricio Caraballo-Rodríguez, Bahar Behsaz, Deepa D. Acharya, Annabell Linck, Pieter C. Dorrestein |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
General Physics and Astronomy Datasets as Topic Peptide 01 natural sciences Genome Mass Spectrometry Drug Discovery Peptide Synthases Soil Microbiology chemistry.chemical_classification Natural products Multidisciplinary Microbiota Nuclear magnetic resonance spectrometry Anti-Bacterial Agents Infectious Diseases Multigene Family Algorithms Metabolic Networks and Pathways Biotechnology Peptide Biosynthesis Science Genomics Computational biology Biology 010402 general chemistry General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Metabolomics Genetics Humans Amino Acid Sequence Gene Data mining Biological Products Human Genome Computational Biology General Chemistry Ribosomal RNA 0104 chemical sciences 030104 developmental biology chemistry Genome mining Metagenomics Peptides Software |
| Zdroj: | Nature communications, vol 12, iss 1 Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) Nature Communications |
| Popis: | Non-Ribosomal Peptides (NRPs) represent a biomedically important class of natural products that include a multitude of antibiotics and other clinically used drugs. NRPs are not directly encoded in the genome but are instead produced by metabolic pathways encoded by biosynthetic gene clusters (BGCs). Since the existing genome mining tools predict many putative NRPs synthesized by a given BGC, it remains unclear which of these putative NRPs are correct and how to identify post-assembly modifications of amino acids in these NRPs in a blind mode, without knowing which modifications exist in the sample. To address this challenge, here we report NRPminer, a modification-tolerant tool for NRP discovery from large (meta)genomic and mass spectrometry datasets. We show that NRPminer is able to identify many NRPs from different environments, including four previously unreported NRP families from soil-associated microbes and NRPs from human microbiota. Furthermore, in this work we demonstrate the anti-parasitic activities and the structure of two of these NRP families using direct bioactivity screening and nuclear magnetic resonance spectrometry, illustrating the power of NRPminer for discovering bioactive NRPs. Current genome mining methods predict many putative non-ribosomal peptides (NRPs) from their corresponding biosynthetic gene clusters, but it remains unclear which of those exist in nature and how to identify their post-assembly modifications. Here, the authors develop NRPminer, a modification-tolerant tool for the discovery of NRPs from large genomic and mass spectrometry datasets, and use it to find 180 NRPs from different environments. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|