Long-Read Metagenome-Assembled Genomes Improve Identification of Novel Complete Biosynthetic Gene Clusters in a Complex Microbial Activated Sludge Ecosystem

Sánchez-Navarro, Roberto; Nuhamunada, Matin; Mohite, Omkar S.; Wasmund, Kenneth; Albertsen, Mads; Gram, Lone; Nielsen, Per Halkjær; Weber, Tilmann; Singleton, Caitlin M.

doi:10.1128/msystems.00632-22

Cited by 22 publications

(18 citation statements)

References 74 publications

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“…Specifically, when BGCs are located on contig edges, their count can be artificially increased when analyzed with antiSMASH as a broken BGC is likely to be counted twice. Thus the number of BGCs on the contig edge is a metric of genome quality for BGC analysis [23]. We identified only 6,524 BGCs (9.2%) situated at contig edges indicating a high quality of the collected dataset at capturing mostly complete BGCs [24].…”

Section: Resultsmentioning

confidence: 99%

Pangenome mining of theStreptomycesgenus redefines their biosynthetic potential

Mohite,

Jørgensen,

Booth

et al. 2024

Preprint

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BackgroundStreptomycesis a highly diverse genus known for the production of secondary or specialized metabolites with a wide range of applications in the medical and agricultural industries. Several thousand complete or nearly-completeStreptomycesgenome sequences are now available, affording the opportunity to deeply investigate the biosynthetic potential within these organisms and to advance natural product discovery initiatives.ResultWe performed pangenome analysis on 2,371Streptomycesgenomes, including approximately 1,200 complete assemblies. Employing a data-driven approach based on genome similarities, theStreptomycesgenus was classified into 7 primary and 42 secondary MASH-clusters, forming the basis for a comprehensive pangenome mining. A refined workflow for grouping biosynthetic gene clusters (BGCs) redefined their diversity across different MASH-clusters. This workflow also reassigned 2,729 known BGC families to only 440 families, a reduction caused by inaccuracies in BGC boundary detections. When the genomic location of BGCs is included in the analysis, a conserved genomic structure (synteny) among BGCs becomes apparent within species and MASH-clusters. This synteny suggests that vertical inheritance is a major factor in the acquisition of new BGCs.ConclusionOur analysis of a genomic dataset at a scale of thousands of genomes refined predictions of BGC diversity using MASH-clusters as a basis for pangenome analysis. The observed conservation in the order of BGCs’ genomic locations showed that the BGCs are vertically inherited. The presented workflow and the in-depth analysis pave the way for large-scale pangenome investigations and enhance our understanding of the biosynthetic potential of theStreptomycesgenus.

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Section: Resultsmentioning

confidence: 99%

Pangenome mining of theStreptomycesgenus redefines their biosynthetic potential

Mohite,

Jørgensen,

Booth

et al. 2024

Preprint

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“…[Kitasatospora] papulosa (10) Streptomyces longwoodensis (10) Streptomyces cellulosae (12) Streptomyces virginiae (12) Streptomyces canus (17) Streptomyces albidoflavus (19) Streptomyces anulatus (31) Other Streptomyces (476)…”

Section: Data Availabilitymentioning

confidence: 99%

“…These features have established genome mining as a complementary approach to the bioactivity and compound-centered discovery of novel bioactive molecules 8 . As some of these BGCs, such as the gargantulide BGC 9 , have sizes of more than 200 kbp, high quality genome assemblies have a strong influence on the quality of the genome mining analyses, as contiguous sequence data allows the identification of complete gene clusters and not just fragments – a challenge that is prevalent with low to medium quality draft genome and many metagenomic datasets 10 .…”

Section: Introductionmentioning

confidence: 99%

A treasure trove of 1,034 actinomycete genomes

Jørgensen,

Mohite,

Sterndorff

et al. 2024

Preprint

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Filamentous Actinobacteria, recently renamed Actinomycetia, are the most prolific source of microbial bioactive natural products. Studies on biosynthetic gene clusters benefit from or require chromosome-level assemblies. Here, we provide DNA sequences from more than 1,000 isolates: 881 complete genomes and 153 near-complete genomes, representing 28 genera and 389 species, including 244 likely novel species. All genomes are from filamentous isolates of the class Actinomycetia from the NBC culture collection. The largest genus is Streptomyces with 886 genomes including 742 complete assemblies. We use this data to show that analysis of complete genomes can bring biological understanding not previously derived from more fragmented sequences or less systematic datasets. We document the central and structured location of core genes and distal location of specialized metabolite biosynthetic gene clusters and duplicate core genes on the linear Streptomyces chromosome, and analyze the content and length of the terminal inverted repeats which are characteristic for Streptomyces. We then analyze the diversity of trans-AT polyketide synthase biosynthetic gene clusters, which encodes the machinery of a biotechnologically highly interesting compound class. These insights have both ecological and biotechnological implications in understanding the importance of high quality genomic resources and the complex role synteny plays in Actinomycetia biology.

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“…BGCs are the genes encoding secondary metabolites (SMs), a cluster of bacterium-originated chemical compounds with bioactivities and diverse structures. As the bridge between microbiome and host, BGCs have proven to be associated with diseases [95] , [96] . Jaeyun Sung et al utilized TaxiBGC on gut microbiome samples from three published case-control studies and found 5 BGCs elevated in CD patients, which encoded for gassericin E, gassericin S, gassericin T, acticin Q and ruminococcin A, respectively [95] .…”

Section: Gut Microbiome In CDmentioning

confidence: 99%

Multi-omics in Crohn's disease: New insights from inside

Zhao

et al. 2023

Computational and Structural Biotechnology Journal

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Long-Read Metagenome-Assembled Genomes Improve Identification of Novel Complete Biosynthetic Gene Clusters in a Complex Microbial Activated Sludge Ecosystem

Cited by 22 publications

References 74 publications

Pangenome mining of theStreptomycesgenus redefines their biosynthetic potential

Pangenome mining of theStreptomycesgenus redefines their biosynthetic potential

A treasure trove of 1,034 actinomycete genomes

Multi-omics in Crohn's disease: New insights from inside

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