Dataset Information

In silico exploration of Red Sea Bacillus genomes for natural product biosynthetic gene clusters.

ABSTRACT:

Background

The increasing spectrum of multidrug-resistant bacteria is a major global public health concern, necessitating discovery of novel antimicrobial agents. Here, members of the genus Bacillus are investigated as a potentially attractive source of novel antibiotics due to their broad spectrum of antimicrobial activities. We specifically focus on a computational analysis of the distinctive biosynthetic potential of Bacillus paralicheniformis strains isolated from the Red Sea, an ecosystem exposed to adverse, highly saline and hot conditions.

Results

We report the complete circular and annotated genomes of two Red Sea strains, B. paralicheniformis Bac48 isolated from mangrove mud and B. paralicheniformis Bac84 isolated from microbial mat collected from Rabigh Harbor Lagoon in Saudi Arabia. Comparing the genomes of B. paralicheniformis Bac48 and B. paralicheniformis Bac84 with nine publicly available complete genomes of B. licheniformis and three genomes of B. paralicheniformis, revealed that all of the B. paralicheniformis strains in this study are more enriched in nonribosomal peptides (NRPs). We further report the first computationally identified trans-acyltransferase (trans-AT) nonribosomal peptide synthetase/polyketide synthase (PKS/ NRPS) cluster in strains of this species.

Conclusions

B. paralicheniformis species have more genes associated with biosynthesis of antimicrobial bioactive compounds than other previously characterized species of B. licheniformis, which suggests that these species are better potential sources for novel antibiotics. Moreover, the genome of the Red Sea strain B. paralicheniformis Bac48 is more enriched in modular PKS genes compared to B. licheniformis strains and other B. paralicheniformis strains. This may be linked to adaptations that strains surviving in the Red Sea underwent to survive in the relatively hot and saline ecosystems.

SUBMITTER: Othoum G

PROVIDER: S-EPMC5964695 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

In silico exploration of Red Sea Bacillus genomes for natural product biosynthetic gene clusters.

Othoum Ghofran G Bougouffa Salim S Razali Rozaimi R Bokhari Ameerah A Alamoudi Soha S Antunes André A Gao Xin X Hoehndorf Robert R Arold Stefan T ST Gojobori Takashi T Hirt Heribert H Mijakovic Ivan I Bajic Vladimir B VB Lafi Feras F FF Essack Magbubah M

BMC genomics 20180522 1

<h4>Background</h4>The increasing spectrum of multidrug-resistant bacteria is a major global public health concern, necessitating discovery of novel antimicrobial agents. Here, members of the genus Bacillus are investigated as a potentially attractive source of novel antibiotics due to their broad spectrum of antimicrobial activities. We specifically focus on a computational analysis of the distinctive biosynthetic potential of Bacillus paralicheniformis strains isolated from the Red Sea, an eco ...[more]

PMID: 29788916

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Project description:BackgroundAntibiotic resistance is a growing problem that can be ameliorated by the discovery of novel drug candidates. Bacterial associates are often the source of pharmaceutically active natural products isolated from marine invertebrates, and thus, important targets for drug discovery. While the microbiomes of many marine organisms have been extensively studied, microbial communities from chemically-rich nudibranchs, marine invertebrates that often possess chemical defences, are relatively unknown.MethodsWe applied both culture-dependent and independent approaches to better understand the biochemical potential of microbial communities associated with nudibranchs. Gram-positive microorganisms isolated from nudibranchs collected in the Red Sea were screened for antibacterial and antitumor activity. To assess their biochemical potential, the isolates were screened for the presence of natural product biosynthetic gene clusters, including polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, using PCR. The microbiomes of the nudibranchs were investigated by high-throughput sequencing of 16S rRNA amplicons.ResultsIn screens against five model microorganisms, 51% of extracts displayed antimicrobial activity against more than one organism, and 19% exhibited antitumor activity against Ehrlich's ascites carcinoma. Sixty-four percent of isolates contained PKS and NRPS genes, suggesting their genomes contain gene clusters for natural product biosynthesis. Thirty-five percent were positive for more than one class of biosynthetic gene. These strains were identified as belonging to the Firmicutes and Actinobacteria phyla via 16S rRNA gene sequencing. In addition, 16S rRNA community amplicon sequencing revealed all bacterial isolates were present in the uncultured host-associated microbiome, although they were a very small percentage of the total community. Taken together, these results indicate that bacteria associated with marine nudibranchs are potentially a rich source of bioactive compounds and natural product biosynthetic genes.

Project description:Microbial specialised metabolism is full of valuable natural products that are applied clinically, agriculturally, and industrially. The genes that encode their biosynthesis are often physically clustered on the genome in biosynthetic gene clusters (BGCs). Many BGCs consist of multiple groups of co-evolving genes called sub-clusters that are responsible for the biosynthesis of a specific chemical moiety in a natural product. Sub-clusters therefore provide an important link between the structures of a natural product and its BGC, which can be leveraged for predicting natural product structures from sequence, as well as for linking chemical structures and metabolomics-derived mass features to BGCs. While some initial computational methodologies have been devised for sub-cluster detection, current approaches are not scalable, have only been run on small and outdated datasets, or produce an impractically large number of possible sub-clusters to mine through. Here, we constructed a scalable method for unsupervised sub-cluster detection, called iPRESTO, based on topic modelling and statistical analysis of co-occurrence patterns of enzyme-coding protein families. iPRESTO was used to mine sub-clusters across 150,000 prokaryotic BGCs from antiSMASH-DB. After annotating a fraction of the resulting sub-cluster families, we could predict a substructure for 16% of the antiSMASH-DB BGCs. Additionally, our method was able to confirm 83% of the experimentally characterised sub-clusters in MIBiG reference BGCs. Based on iPRESTO-detected sub-clusters, we could correctly identify the BGCs for xenorhabdin and salbostatin biosynthesis (which had not yet been annotated in BGC databases), as well as propose a candidate BGC for akashin biosynthesis. Additionally, we show for a collection of 145 actinobacteria how substructures can aid in linking BGCs to molecules by correlating iPRESTO-detected sub-clusters to MS/MS-derived Mass2Motifs substructure patterns. This work paves the way for deeper functional and structural annotation of microbial BGCs by improved linking of orphan molecules to their cognate gene clusters, thus facilitating accelerated natural product discovery.

Dataset Information

In silico exploration of Red Sea Bacillus genomes for natural product biosynthetic gene clusters.

Background

Results

Conclusions

Publications

In silico exploration of Red Sea Bacillus genomes for natural product biosynthetic gene clusters.

Similar Datasets

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