A computational framework to explore large-scale biosynthetic diversity

Navarro-Muñoz, Jorge C.; Sélem-Mójica, Nelly; Mullowney, Michael W.; Kautsar, Satria A.; Tryon, James H.; Parkinson, Elizabeth I.; Santos, Emmanuel L. C. de los; Yeong, Marley; Cruz-Morales, Pablo; Abubucker, Sahar; Roeters, Arne; Lokhorst, Wouter; Fernàndez-Guerra, Antonio; Cappelini, Luciana Teresa Dias; Goering, Anthony W.; Thomson, Regan J.; Metcalf, William W.; Kelleher, Neil L.; Barona‐Gómez, Francisco; Medema, Marnix H.

doi:10.1038/s41589-019-0400-9

Cited by 537 publications

(521 citation statements)

References 59 publications

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“…A multi-locus phylogeny of all SGB representatives was inferred with PhyloPhlan v.0.41 19 . Secondary metabolites were identified with AntiSMASH v.5.1.1 20 and DeepBGC v.0.1.18 21 and then characterized with BiGSCAPE 22 . Abricate was used to identify antimicrobial resistance genes.…”

Section: Metagenome Assembly Of Genomes Pipelinementioning

confidence: 99%

Large scale metagenome assembly reveals novel animal-associated microbial genomes, biosynthetic gene clusters, and other genetic diversity

Youngblut

Cuesta-Zuluaga

Reischer

et al. 2020

Preprint

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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 4374 metagenome assembled genomes (MAGs) from gut samples of 180 predominantly wild animal species representing 5 classes. Combined with existing datasets, we produced 5596 non-redundant, quality MAGs and 1522 species-level genome bins (SGBs). Most SGBs were novel at the species, genus, or family levels, 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 1986 diverse and largely novel biosynthetic gene clusters. Gene-based assembly revealed tremendous gene diversity, much of it host or environment specific. Our MAG and gene datasets greatly expand the microbial genome repertoire and provide a broad view of microbial adaptations to life within a living host.

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Section: Metagenome Assembly Of Genomes Pipelinementioning

confidence: 99%

Large scale metagenome assembly reveals novel animal-associated microbial genomes, biosynthetic gene clusters, and other genetic diversity

Youngblut

Cuesta-Zuluaga

Reischer

et al. 2020

Preprint

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“…Node support comes from 10000 bootstrap generations. For analysis of the genome context of the selected ECF56 homologs shown in figure 3 we used CORASON with an adhoc genomes database including selected organisms (50). the parameters for the search were e-value 1E-12 and bit-score cutoff of 200, the graphical output was modified to follow the order of a phylogenetic tree generated with the protein sequences homologs identified by CORASON with identical parameters to those described above.…”

Section: Methodsmentioning

confidence: 99%

Characterization of an ECF56-family sigma factor fromStreptomyces venezuelaereveals a highly conserved regulome

Thompson

Zargar

Cruz-Morales

et al. 2020

Preprint

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34Bacteria often possess alternative sigma factors that initiate the transcription of 35 specific genes under environmental stresses, the largest and most diverse group being 36 the extracytoplasmic function (ECF) sigma factors. The regulation of ECF activity is 37 crucial for ensuring the distinct transcription of stress responsive genes only occurs 38 under the appropriate conditions. While most ECFs are comprised of only the core σ 2 39 and σ 4 regions, a unique form of ECF sigma factor regulation also contains a C-terminal 40 extension bearing homology to the NTF2 superfamily of protein domains. While 41 previous work has shown that this NTF2 domain can affect transcriptional activity in vivo 42 in ECF41 and ECF42, its role in the newly classified ECF56 subgroup is unknown. In 43 this work, we show that truncation of the C-terminus of the ECF56 sigma factor 44 SVEN_4562 of Streptomyces venezuelae upregulates its activity in a hybrid assay. 45 Through transcriptomics in S. venezuelae, we found that this truncated ECF56 sigma 46 factor has a highly conserved promoter sequence in vivo. Bioinformatic assays 47 ECF56 family of sigma factors is highly conserved and performs important functions yet 53 to be understood in Actinobacteria. 54 55 Importance 56 Most ECF sigma-factors rely on anti-sigma factor regulation; in contrast, the 57 unique classes of ECF sigma-factors that contain a C-terminal extension are thought to 58 respond directly to an environmental signal. Here we show that the cis-acting regulatory 59 element of the ECF56 regulon is likely highly conserved in many Actinobacteria, with 60 exact nucleotide level conservation over ~2 billion years of evolution. The high 61 conservation of this genetic architecture, as well as a conserved gene content within the 62 regulon, strongly point to a specialized and important role in Actinobacteria biology. 63 64

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“…Subsequently, the corresponding Genbank file of the flanking region was downloaded. The resulting Genbank file collection was used as an input for BiG-SCAPE 28 , which groups metabolic gene clusters (MGCs) into families. The output networks were visualized using the BiG-SCAPE interactive visualization tool.…”

Section: Analysis Of the Genomic Context Of Fe-s Flavoenzymesmentioning

confidence: 99%

Computational genomic discovery of diverse gene clusters harboring Fe-S flavoenzymes in anaerobic gut microbiota

Fischbach

Medema

2020

Preprint

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The gut contains an enormous diversity of simple as well as complex molecules from highly diverse food sources as well as host-secreted molecules. This presents a large metabolic opportunity for the gut microbiota, but little is known on how gut microbes are able to catabolize this large chemical diversity. Recently, Fe-S flavoenzymes were found to be key in the transformation of bile acids, catalysing the key step in the 7 -dehydroxylation pathway that allows gut bacteria to transform cholic acid (CA) into deoxycholic acid (DCA), an exclusively microbe-derived molecule with major implications for human health. While this enzyme family has also been implicated in a limited number of other catalytic transformations, little is known about the extent to which it is of more global importance in gut microbial metabolism. Here, we use large-scale computational genomic analysis to show that this enzyme superfamily has undergone a remarkable expansion in Clostridiales, and occurs throughout a diverse array of >1,000 different families of putative metabolic gene clusters. Analysis of the enzyme content of these gene clusters suggests that they encode pathways with a wide range of predicted substrate classes, including saccharides, amino acids/peptides and lipids. Altogether, these results indicate a potentially important role of this protein superfamily in the human gut, and our dataset provides significant opportunities for the discovery of novel pathways that may have significant effects on human health.

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A computational framework to explore large-scale biosynthetic diversity

Cited by 537 publications

References 59 publications

Large scale metagenome assembly reveals novel animal-associated microbial genomes, biosynthetic gene clusters, and other genetic diversity

Large scale metagenome assembly reveals novel animal-associated microbial genomes, biosynthetic gene clusters, and other genetic diversity

Characterization of an ECF56-family sigma factor fromStreptomyces venezuelaereveals a highly conserved regulome

Computational genomic discovery of diverse gene clusters harboring Fe-S flavoenzymes in anaerobic gut microbiota

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