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• W2899484106 abstract "The gut microbiota has strong potential to biosynthesize large amounts of structurally distinct metabolites with a variety of biological activities that are promising drugs and drug candidates. Only a fraction of the gut microbiota have been cultivated so far, which makes it even more important to investigate microbial ‘dark matter’, which is a promising source for drug discovery. One emerging approach is to develop metabolomics data sets and to construct metabolic network models by machine learning for both clinics and laboratories. The boundary between genome/metagenomics-based, culture-based, and metabolomics-based mining approaches is fading and it is becoming feasible to combine two or more strategies to accelerate the mining of bioactive metabolites in the future. The mammalian gut has a remarkable abundance of microbes. These microbes have strong potential to biosynthesize distinct metabolites that are promising drugs, and many more bioactive compounds have yet to be explored as potential drug candidates. These small bioactive molecules often mediate important host–microbe and microbe–microbe interactions. In this review, we provide perspectives on and challenges associated with three mining strategies – culture-based, (meta)genomics-based, and metabolomics-based mining approaches – for discovering natural products derived from biosynthetic gene clusters (BGCs) in mammalian gut microbiota. In addition, we comprehensively summarize the structures, biological functions, and BGCs of these compounds. Improving these techniques, including by using combinatorial approaches, may accelerate drug discovery from gut microbes. The mammalian gut has a remarkable abundance of microbes. These microbes have strong potential to biosynthesize distinct metabolites that are promising drugs, and many more bioactive compounds have yet to be explored as potential drug candidates. These small bioactive molecules often mediate important host–microbe and microbe–microbe interactions. In this review, we provide perspectives on and challenges associated with three mining strategies – culture-based, (meta)genomics-based, and metabolomics-based mining approaches – for discovering natural products derived from biosynthetic gene clusters (BGCs) in mammalian gut microbiota. In addition, we comprehensively summarize the structures, biological functions, and BGCs of these compounds. Improving these techniques, including by using combinatorial approaches, may accelerate drug discovery from gut microbes. group of genes in a genome that encodes a biosynthetic pathway to produce a specialized metabolite in bacteria, fungi, and plants. technology in which the targeting fragment is digested from bacterial chromosomes in vitro by the RNA-guided Cas9 nuclease at two designated loci and cloned to the vector by Gibson assembly. essential adaptive immunity system in certain bacteria and archaea, enabling the organisms to respond to and eliminate invading genetic material. Based on these technologies, it is possible to effectively and specifically change genes within organisms. culturing approach that uses multiple culture conditions and MALDI–TOF and 16S rRNA to rapidly identify large numbers of colonies. novel technique that links functional genes and phylogenetic markers in uncultured single cells that cost-effectively provides a throughput of hundreds of thousands of cells. combining in vitro exonuclease and annealing with the remarkable capacity of full length RecET homologous recombination to retrieve specified regions from genomic DNA preparations, this method bypasses DNA library construction and screening. aligning and merging fragments from a longer DNA sequence to reconstruct the original sequence. process of grouping reads or contigs and assigning them to operational taxonomic units. web tool that enables a systematic investigation of monophyletic genomes to detect significantly enriched groups of homologous genes between one taxon and another. peptide secondary metabolites from bacteria and fungi with a variety of medicinal properties synthesized by enzymes called nonribosomal peptide synthetases (NRPSs) and a series of tailoring enzymes, in which ribosomal machineries and messenger RNAs do not play a role. natural products found in a variety of organisms, including plants, fungi, and bacteria, which are produced by the polymerization of acyl-coenzyme A by PK synthase enzymes and a series of tailoring enzymes, including transport, regulatory, and modifying enzymes. in vivo reaction and based either on the red genes of the lambda phage or the recE/recT genes of the Rac prophage. Redα or RecE act as a 5′ → 3′ exonuclease and Redβ or RecT as a single strand DNA binding protein. novel approach to link 16s rRNA amplicon profiles to metagenomes that enable capturing both ribosomal RNA variable regions and their flanking protein-coding genes simultaneously. natural products produced by ribosomes with molecular weight less than 1000 Da that undergo chemical transformations after translation. They are biosynthesized by precursor peptides and a series of enzymes, including immune factors and transport, regulatory, and modifying enzymes. platform that drives bacteria to express and self-test peptides of any size, structure, or sequence complexity for antimicrobial activity. It is a high-throughput screening platform that rapidly identifies lead antimicrobial peptides to combat multidrug-resistant Gram-negative bacteria. ribosomally produced peptides with post-translationally installed thiazole and oxazole heterocycles derived from cysteine, serine, and threonine residues." @default.
• W2899484106 created "2018-11-09" @default.
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• W2899484106 date "2019-05-01" @default.
• W2899484106 modified "2023-10-18" @default.
• W2899484106 title "Natural Products from Mammalian Gut Microbiota" @default.
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• W2899484106 doi "https://doi.org/10.1016/j.tibtech.2018.10.003" @default.
• W2899484106 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30392727" @default.
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