Expansion of RiPP biosynthetic space through integration of pan-genomics and machine learning uncovers a novel class of lantibiotics
| العنوان: | Expansion of RiPP biosynthetic space through integration of pan-genomics and machine learning uncovers a novel class of lantibiotics |
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| المؤلفون: | Peter Cimermancic, Michael A. Fischbach, Alexander M. Kloosterman, Somayah S. Elsayed, Gilles P. van Wezel, Marnix H. Medema, Michalis Hadjithomas, Mohamed S. Donia, Chao Du |
| المصدر: | PloS Biology, 18 PLoS Biology, Vol 18, Iss 12, p e3001026 (2020) PLoS Biology PloS Biology 18 (2020) PLoS Biology, 18(12), e3001026 |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Subfamily, Pathology and Laboratory Medicine, Biochemistry, 01 natural sciences, Genome, Machine Learning, Bacteriocins, Gene cluster, Medicine and Health Sciences, Amino Acids, Biology (General), Dehydration (Medicine), Fungal Pathogens, Enzyme Precursors, Organic Compounds, General Neuroscience, Methods and Resources, Genomics, Streptomyces, Chemistry, Medical Microbiology, Multigene Family, Physical Sciences, Identification (biology), Pathogens, General Agricultural and Biological Sciences, Algorithms, QH301-705.5, Bioinformatics, Gene prediction, Protein domain, Mycology, Computational biology, Biology, 010402 general chemistry, Microbiology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Signs and Symptoms, Protein Domains, Bioinformatica, Genetics, Life Science, Sulfur Containing Amino Acids, Cysteine, Gene Prediction, Microbial Pathogens, Gene, Biological Products, General Immunology and Microbiology, Organic Chemistry, Chemical Compounds, Computational Biology, Biology and Life Sciences, Proteins, Genome Analysis, 0104 chemical sciences, 030104 developmental biology, Enzymology, Clinical Medicine, EPS, Peptides, Protein Processing, Post-Translational, Ribosomes |
| الوصف: | Microbial natural products constitute a wide variety of chemical compounds, many which can have antibiotic, antiviral, or anticancer properties that make them interesting for clinical purposes. Natural product classes include polyketides (PKs), nonribosomal peptides (NRPs), and ribosomally synthesized and post-translationally modified peptides (RiPPs). While variants of biosynthetic gene clusters (BGCs) for known classes of natural products are easy to identify in genome sequences, BGCs for new compound classes escape attention. In particular, evidence is accumulating that for RiPPs, subclasses known thus far may only represent the tip of an iceberg. Here, we present decRiPPter (Data-driven Exploratory Class-independent RiPP TrackER), a RiPP genome mining algorithm aimed at the discovery of novel RiPP classes. DecRiPPter combines a Support Vector Machine (SVM) that identifies candidate RiPP precursors with pan-genomic analyses to identify which of these are encoded within operon-like structures that are part of the accessory genome of a genus. Subsequently, it prioritizes such regions based on the presence of new enzymology and based on patterns of gene cluster and precursor peptide conservation across species. We then applied decRiPPter to mine 1,295 Streptomyces genomes, which led to the identification of 42 new candidate RiPP families that could not be found by existing programs. One of these was studied further and elucidated as a representative of a novel subfamily of lanthipeptides, which we designate class V. The 2D structure of the new RiPP, which we name pristinin A3 (1), was solved using nuclear magnetic resonance (NMR), tandem mass spectrometry (MS/MS) data, and chemical labeling. Two previously unidentified modifying enzymes are proposed to create the hallmark lanthionine bridges. Taken together, our work highlights how novel natural product families can be discovered by methods going beyond sequence similarity searches to integrate multiple pathway discovery criteria. This study shows that decRiPPter, an innovative algorithmic approach using pan-genomics and machine learning, can discover novel types of ribosomally synthesized peptide (RIPP) natural products, including a new class of lanthipeptides. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1544-9173 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::412e65b2c866ff42f148c76879df05d5 https://research.wur.nl/en/publications/expansion-of-ripp-biosynthetic-space-through-integration-of-pan-g |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....412e65b2c866ff42f148c76879df05d5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15449173 |
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