Dataset Information

BiosyntheticSPAdes: reconstructing biosynthetic gene clusters from assembly graphs.

ABSTRACT: Predicting biosynthetic gene clusters (BGCs) is critically important for discovery of antibiotics and other natural products. While BGC prediction from complete genomes is a well-studied problem, predicting BGCs in fragmented genomic assemblies remains challenging. The existing BGC prediction tools often assume that each BGC is encoded within a single contig in the genome assembly, a condition that is violated for most sequenced microbial genomes where BGCs are often scattered through several contigs, making it difficult to reconstruct them. The situation is even more severe in shotgun metagenomics, where the contigs are often short, and the existing tools fail to predict a large fraction of long BGCs. While it is difficult to assemble BGCs in a single contig, the structure of the genome assembly graph often provides clues on how to combine multiple contigs into segments encoding long BGCs. We describe biosyntheticSPAdes, a tool for predicting BGCs in assembly graphs and demonstrate that it greatly improves the reconstruction of BGCs from genomic and metagenomics data sets.

SUBMITTER: Meleshko D

PROVIDER: S-EPMC6673720 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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BiosyntheticSPAdes: reconstructing biosynthetic gene clusters from assembly graphs.

Meleshko Dmitry D Mohimani Hosein H Tracanna Vittorio V Hajirasouliha Iman I Medema Marnix H MH Korobeynikov Anton A Pevzner Pavel A PA

Genome research 20190603 8

Predicting biosynthetic gene clusters (BGCs) is critically important for discovery of antibiotics and other natural products. While BGC prediction from complete genomes is a well-studied problem, predicting BGCs in fragmented genomic assemblies remains challenging. The existing BGC prediction tools often assume that each BGC is encoded within a single contig in the genome assembly, a condition that is violated for most sequenced microbial genomes where BGCs are often scattered through several co ...[more]

PMID: 31160374

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Project description:BackgroundBiosynthetic gene clusters produce a wide range of metabolites with activities that are of interest to the pharmaceutical industry. Specific interest is shown towards those metabolites that exhibit antimicrobial activities against multidrug-resistant bacteria that have become a global health threat. Genera of the phylum Firmicutes are frequently identified as sources of such metabolites, but the biosynthetic potential of its Virgibacillus genus is not known. Here, we used comparative genomic analysis to determine whether Virgibacillus strains isolated from the Red Sea mangrove mud in Rabigh Harbor Lagoon, Saudi Arabia, may be an attractive source of such novel antimicrobial agents.ResultsA comparative genomics analysis based on Virgibacillus dokdonensis Bac330, Virgibacillus sp. Bac332 and Virgibacillus halodenitrificans Bac324 (isolated from the Red Sea) and six other previously reported Virgibacillus strains was performed. Orthology analysis was used to determine the core genomes as well as the accessory genome of the nine Virgibacillus strains. The analysis shows that the Red Sea strain Virgibacillus sp. Bac332 has the highest number of unique genes and genomic islands compared to other genomes included in this study. Focusing on biosynthetic gene clusters, we show how marine isolates, including those from the Red Sea, are more enriched with nonribosomal peptides compared to the other Virgibacillus species. We also found that most nonribosomal peptide synthases identified in the Virgibacillus strains are part of genomic regions that are potentially horizontally transferred.ConclusionsThe Red Sea Virgibacillus strains have a large number of biosynthetic genes in clusters that are not assigned to known products, indicating significant potential for the discovery of novel bioactive compounds. Also, having more modular synthetase units suggests that these strains are good candidates for experimental characterization of previously identified bioactive compounds as well. Future efforts will be directed towards establishing the properties of the potentially novel compounds encoded by the Red Sea specific trans-AT PKS/NRPS cluster and the type III PKS/NRPS cluster.

Project description:Large-scale metagenome assemblies of human microbiomes have produced a vast catalogue of previously unseen microbial genomes; however, comparatively few microbial genomes derive from other vertebrates. Here, we generated 5,596 metagenome-assembled genomes (MAGs) from the gut metagenomes of 180 predominantly wild animal species representing 5 classes, in addition to 14 existing animal gut metagenome data sets. The MAGs comprised 1,522 species-level genome bins (SGBs), most of which were novel at the species, genus, or family level, and the majority were enriched in host versus environment metagenomes. Many traits distinguished SGBs enriched in host or environmental biomes, including the number of antimicrobial resistance genes. We identified 1,986 diverse biosynthetic gene clusters; only 23 clustered with any MIBiG database references. Gene-based assembly revealed tremendous gene diversity, much of it host or environment specific. Our MAG and gene data sets greatly expand the microbial genome repertoire and provide a broad view of microbial adaptations to the vertebrate gut.IMPORTANCE Microbiome studies on a select few mammalian species (e.g., humans, mice, and cattle) have revealed a great deal of novel genomic diversity in the gut microbiome. However, little is known of the microbial diversity in the gut of other vertebrates. We studied the gut microbiomes of a large set of mostly wild animal species consisting of mammals, birds, reptiles, amphibians, and fish. Unfortunately, we found that existing reference databases commonly used for metagenomic analyses failed to capture the microbiome diversity among vertebrates. To increase database representation, we applied advanced metagenome assembly methods to our animal gut data and to many public gut metagenome data sets that had not been used to obtain microbial genomes. Our resulting genome and gene cluster collections comprised a great deal of novel taxonomic and genomic diversity, which we extensively characterized. Our findings substantially expand what is known of microbial genomic diversity in the vertebrate gut.

Dataset Information

BiosyntheticSPAdes: reconstructing biosynthetic gene clusters from assembly graphs.

Publications

BiosyntheticSPAdes: reconstructing biosynthetic gene clusters from assembly graphs.

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