Search Results - "BRADY, Sean F"
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Culture-independent discovery of natural products from soil metagenomes
Published in Journal of industrial microbiology & biotechnology (01-03-2016)“…Bacterial natural products have proven to be invaluable starting points in the development of many currently used therapeutic agents. Unfortunately,…”
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Discovery of indolotryptoline antiproliferative agents by homology-guided metagenomic screening
Published in Proceedings of the National Academy of Sciences - PNAS (12-02-2013)“…Natural product discovery by random screening of broth extracts derived from cultured bacteria often suffers from high rates of redundant isolation, making it…”
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Functional analysis of environmental DNA-derived type II polyketide synthases reveals structurally diverse secondary metabolites
Published in Proceedings of the National Academy of Sciences - PNAS (02-08-2011)“…A single gram of soil is predicted to contain thousands of unique bacterial species. The majority of these species remain recalcitrant to standard culture…”
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Yeast homologous recombination-based promoter engineering for the activation of silent natural product biosynthetic gene clusters
Published in Proceedings of the National Academy of Sciences - PNAS (21-07-2015)“…Large-scale sequencing of prokaryotic (meta)genomic DNA suggests that most bacterial natural product gene clusters are not expressed under common laboratory…”
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Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist
Published in Proceedings of the National Academy of Sciences - PNAS (01-09-2015)“…The trillions of bacteria that make up the human microbiome are believed to encode functions that are important to human health; however, little is known about…”
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Discovery of MRSA active antibiotics using primary sequence from the human microbiome
Published in Nature chemical biology (01-12-2016)“…The synthetic bioinformatic natural products (syn-BNPs) approach identifies putative natural products that are validated directly by independent synthesis. Its…”
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Uncovering the biosynthetic potential of rare metagenomic DNA using co-occurrence network analysis of targeted sequences
Published in Nature communications (26-08-2019)“…Sequencing of DNA extracted from environmental samples can provide key insights into the biosynthetic potential of uncultured bacteria. However, the high…”
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Lapcin, a potent dual topoisomerase I/II inhibitor discovered by soil metagenome guided total chemical synthesis
Published in Nature communications (11-02-2022)“…In natural product discovery programs, the power of synthetic chemistry is often leveraged for the total synthesis and diversification of characterized…”
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Recent application of metagenomic approaches toward the discovery of antimicrobials and other bioactive small molecules
Published in Current opinion in microbiology (01-10-2010)“…Abstract Bacteria grown in pure culture have been the starting point for the discovery of many of the antibacterials now in use. Metagenomics, which utilizes…”
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Tetarimycin A, an MRSA-Active Antibiotic Identified through Induced Expression of Environmental DNA Gene Clusters
Published in Journal of the American Chemical Society (05-12-2012)“…The propagation of DNA extracted directly from environmental samples in laboratory-grown bacteria provides a means to study natural products encoded in the…”
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Chemical-biogeographic survey of secondary metabolism in soil
Published in Proceedings of the National Academy of Sciences - PNAS (11-03-2014)“…In this study, we compare biosynthetic gene richness and diversity of 96 soil microbiomes from diverse environments found throughout the southwestern and…”
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Multiplexed mobilization and expression of biosynthetic gene clusters
Published in Nature communications (06-09-2022)“…Bacterial genomes contain large reservoirs of biosynthetic gene clusters (BGCs) that are predicted to encode unexplored natural products. Heterologous…”
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Mapping gene clusters within arrayed metagenomic libraries to expand the structural diversity of biomedically relevant natural products
Published in Proceedings of the National Academy of Sciences - PNAS (16-07-2013)“…Complex microbial ecosystems contain large reservoirs of unexplored biosynthetic diversity. Here we provide an experimental framework and data analysis tool to…”
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High-throughput retrieval of target sequences from complex clone libraries using CRISPRi
Published in Nature biotechnology (01-05-2023)“…The capture of metagenomic DNA in large clone libraries provides the opportunity to study microbial diversity that is inaccessible using culture-dependent…”
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Multiplexed metagenome mining using short DNA sequence tags facilitates targeted discovery of epoxyketone proteasome inhibitors
Published in Proceedings of the National Academy of Sciences - PNAS (07-04-2015)“…In molecular evolutionary analyses, short DNA sequences are used to infer phylogenetic relationships among species. Here we apply this principle to the study…”
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Rifamycin congeners kanglemycins are active against rifampicin-resistant bacteria via a distinct mechanism
Published in Nature communications (08-10-2018)“…Rifamycin antibiotics (Rifs) target bacterial RNA polymerases (RNAPs) and are widely used to treat infections including tuberculosis. The utility of these…”
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Fluostatins Produced by the Heterologous Expression of a TAR Reassembled Environmental DNA Derived Type II PKS Gene Cluster
Published in Journal of the American Chemical Society (01-09-2010)“…Culture independent approaches for accessing small molecules produced by uncultured bacteria are often hampered by the inability to easily clone environmental…”
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Cloning and characterization of new glycopeptide gene clusters found in an environmental DNA megalibrary
Published in Proceedings of the National Academy of Sciences - PNAS (11-11-2008)“…Glycopeptide antibiotics have long served as drugs of last resort for the treatment of antibiotic-resistant Gram-positive bacterial infections. Resistance to…”
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Unraveling function and diversity of bacterial lectins in the human microbiome
Published in Nature communications (03-06-2022)“…The mechanisms by which commensal organisms affect human physiology remain poorly understood. Lectins are non-enzymatic carbohydrate binding proteins that all…”
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Targeted Metagenomics: Finding Rare Tryptophan Dimer Natural Products in the Environment
Published in Journal of the American Chemical Society (13-05-2015)“…Natural product discovery from environmental genomes (metagenomics) has largely been limited to the screening of existing environmental DNA (eDNA) libraries…”
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