Publications by authors named "Nishanth J Merwin"
Article Synopsis
- Novel antibiotics are urgently needed due to the global issue of antibiotic resistance, with most existing ones coming from microbial secondary metabolism.
- PRISM 4 is a new platform that predicts the chemical structures of antibiotics encoded in bacterial genomes, helping to find new natural antibiotics.
- The platform has been used to analyze over 10,000 bacterial genomes, uncovering thousands of potential new antibiotics, and is accessible for free online.
Microbial natural products represent a rich resource of evolved chemistry that forms the basis for the majority of pharmacotherapeutics. Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a particularly interesting class of natural products noted for their unique mode of biosynthesis and biological activities. Analyses of sequenced microbial genomes have revealed an enormous number of biosynthetic loci encoding RiPPs but whose products remain cryptic.
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- - The study focuses on tRNA-derived cyclodipeptides, which are small molecules known for their beneficial biological activities, but there's a lack of tools to connect specific synthases in bacteria to the cyclodipeptides they produce.
- - Researchers developed a new pipeline to identify and classify gene clusters related to cyclodipeptides across over 93,000 prokaryotic genomes, helping to predict what these peptides might look like and how they’re made.
- - Their findings reveal a significant amount of unexplored chemical potential within prokaryotic genomes, and the created mapping tool serves as a resource for discovering new cyclodipeptides in future research.
Covering: 2000 to 2017Decades of research on human microbiota have revealed much of their taxonomic diversity and established their direct link to health and disease. However, the breadth of bioactive natural products secreted by our microbial partners remains unknown. Of particular interest are antibiotics produced by our microbiota to ward off invasive pathogens.
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- Microbial natural products are valuable for pharmaceuticals and industry, but many remain undiscovered due to complex biosynthetic gene clusters.
- The PRISM (PRediction Informatics for Secondary Metabolomes) project has been revamped with a new algorithm (PRISM 3) that models natural products as chemical graphs, predicting structures for various compounds and expanding to 22 cluster types.
- Key improvements in PRISM 3 include enhanced user experience, faster processing on a large server grid, and better detection of genetic sequences, making natural product discovery more efficient.
Article Synopsis
- * Despite genome sequencing showing many genetically encoded natural products are still unknown, existing bioinformatics tools have been developed to predict nonribosomal peptides and polyketides from sequence data, while RiPPs remain poorly understood due to their complexity.
- * The study introduces a new algorithm that catalogs RiPP biosynthetic gene clusters, uncovering 30,261 RiPP clusters from over 65,000 prokaryotic genomes, leading to the identification of a rare