BAGEL4: a user-friendly web server to thoroughly mine RiPPs and bacteriocins

Heel, Auke J. van; Jong, Anne de; Cui, Song; Viel, Jakob; Kok, Jan; Kuipers, Oscar P.

doi:10.1093/nar/gky383

Cited by 708 publications

(520 citation statements)

References 19 publications

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“…Clusters of precursor peptides with 20 or more members are numbered and sequence logos for these clusters are presented in Supplementary Figure S3. Clusters with characterized members as determined by using BAGEL4 [27] and the MIBiG repository [85] ( Supplementary Table S5) are labeled by a selected member.…”

Section: Phylogenetic Analysis Of Lanc and Lanc-like Domainsmentioning

confidence: 99%

“…Genome-mining studies based on these enzymes have revealed that lanthipeptide BGCs are distributed widely across bacterial phyla [19][20][21][22][23][24][25][26][27][28][29]. Despite the success in bioinformatically identifying likely lanthipeptide BGCs, it has been an outstanding challenge to perform high-throughput analysis of the precursor peptides encoded in these gene clusters.…”

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confidence: 99%

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Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family

Walker

Mitchell

Donk

2020

Preprint

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BackgroundLanthipeptides belong to the ribosomally synthesized and post-translationally modified peptide group of natural products and have a variety of biological activities ranging from antibiotics to antinociceptives. These peptides are cyclized through thioether crosslinks and can bear other secondary post-translational modifications. While lanthipeptide biosynthetic gene clusters can be identified by the presence of characteristic enzymes involved in the post-translational modification of these peptides, locating the precursor peptides encoded within these clusters is challenging due to their short length and high sequence variability, which limits the high-throughput exploration of lanthipeptide precursor peptides. To address this challenge, we enhanced the predictive capabilities of Rapid ORF Description & Evaluation Online (RODEO) to identify all known classes of lanthipeptides. ResultsUsing RODEO, we mined over 100,000 bacterial and archaeal genomes in the RefSeq database. We identified nearly 8,500 lanthipeptide precursor peptides. These precursor peptides were identified in a broad range of bacterial phyla as well as the Euryarchaeota phylum of archaea. Bacteroidetes were found to encode a large number of these biosynthetic gene clusters, despite making up a relatively small portion of the genomes in this dataset. While a number of these precursor peptides are similar to those of previously characterized lanthipeptides, even more were not, including potential antibiotics. Additionally, examination of the biosynthetic gene clusters revealed enzymes that install secondary post-translational modifications are more widespread than initially thought. ConclusionLanthipeptide biosynthetic gene clusters are more widely distributed and the precursor peptides encoded within these clusters are more diverse than previously appreciated, demonstrating that the lanthipeptide sequence-function space remains largely underexplored.

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Section: Phylogenetic Analysis Of Lanc and Lanc-like Domainsmentioning

confidence: 99%

mentioning

confidence: 99%

Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family

Walker

Mitchell

Donk

2020

Preprint

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“…Genome mining for secondary metabolites in all 45 genomes was performed with antiSMASH 5.0 (https://antismash. secondarymetabolites.org, Blin et al, 2017), and BAGEL 4 (http://bagel4.molgenrug.nl/, van Heel et al, 2018). In total, 20 of the known biosynthetic gene clusters (BGCs) listed in the MIIBiG data bank (Medema et al, 2015) were identified.…”

Section: Occurrence Of Gene Clusters Involved In Antagonistic Activitymentioning

confidence: 99%

Cold‐adapted Bacilli isolated from the Qinghai–Tibetan Plateau are able to promote plant growth in extreme environments

Xie

et al. 2019

Environmental Microbiology

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Summary Nearly 1400 Bacillus strains growing in the plant rhizosphere were sampled from different sites on the Qinghai–Tibetan Plateau. Forty‐five of the isolates, selected due to their biocontrol activity, were genome‐sequenced and their taxonomic identification revealed that they were representatives of the Bacillus subtilis species complex (20) and the Bacillus cereus group (9). Majority of the remaining strains were found closely related to Bacillus pumilus, but their average nucleotide identity based on BLAST and electronic DNA/DNA hybridization values excluded closer taxonomic identification. A total of 45 different gene clusters involved in synthesis of secondary metabolites were detected by mining the genomes of the 45 selected strains. Except eight mesophilic strains, the 37 remaining strains were found either cold‐adapted or psychrophilic, able to propagate at 10°C and below (Bacillus wiedmannii NMSL88 and Bacillus sp. RJGP41). Pot experiments performed at 10°C with winter wheat seedlings revealed that cold‐adapted representatives of B. pumilus, B. safensis and B. atrophaeus promoted growth of the seedlings under cold conditions, suggesting that these bacilli isolated from a cold environment are promising candidates for developing of bioformulations useful for application in sustainable agriculture under environmental conditions unfavourable for the mesophilic bacteria presently in use.

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“…First, the Interpro descriptions of the peptidase (IPR005074) and the radical SAM enzyme (IPR023885) indicate a possible involvement in bacteriocin processing and biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPP) [61], respectively. Second, an analysis with indicated that the ubiquitin-activating enzyme had homology to a putative bacteriocin biosynthesis protein from Streptococcus thermophilus (Q5LXQ2), and labelled the contig as potentially containing a sactipeptide [62]. Finally, TonB-dependent receptors, lipoproteins, radical SAM enzymes are common components of bacteriocin biosynthesis clusters and acylation is often observed during bacteriocin biosynthesis [63, 64].…”

Section: Resultsmentioning

confidence: 99%

Anin silicosurvey ofClostridioides difficileextrachromosomal elements

Hornung

Kuijper

Smits

2019

Preprint

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19The gram-positive enteropathogen Clostridioides difficile is the major cause of healthcare 20 associated diarrhoea and is also an important cause of community-acquired infectious 21 diarrhoea. Considering the burden of the disease, many studies have employed whole 22 genome sequencing to identify factors that contribute to virulence and pathogenesis. Though 23 extrachromosomal elements such as plasmids are important for these processes in other 24 bacteria, the few characterized plasmids of C. difficile have no relevant functions assigned 25 and no systematic identification of plasmids has been carried out to date. Here, we perform 26 an in silico analysis of publicly available sequence data, to show that ~13% of all C. difficile 27 strains contain extrachromosomal elements, with 1-6 elements per strain. Our approach 28 identifies known plasmids (e.g. pCD6, pCD630 and cloning plasmids) and 6 novel putative 29 plasmid families. Our study shows that plasmids are abundant and may encode functions 30 that are relevant for C. difficile physiology. The newly identified plasmids may also form the 31 basis for the construction of novel cloning plasmids for C. difficile that are compatible with 32 existing tools. 33 35 36Clostridioides difficile (Clostridium difficile) [1] is a gram-positive, endospore forming, 37 anaerobic bacterium. It is an opportunistic pathogen in humans, and is the causative agent 38 of most cases of antibiotic associated diarrhoea [2]. In recent years, the bacterium is also 39 increasingly found in cases of infectious diarrhoea that cannot be linked to healthcare 40 exposure [2]. C. difficile infections can be refractory to antimicrobial therapy and even when 41 initial cure is observed, relapses are frequent [2]. Typing methods for C. difficile include 42 (capillary) PCR ribotyping, multilocus sequence typing (MLST) and single nucleotide 43 polymorphism (SNP) typing after whole genome sequencing [3]. Since the beginning of the 44 21 th century, an increase in C. difficile infections due to epidemic types such as PCR 45 ribotype 027 and 078 has been noted [4, 5]. Although the molecular mechanisms underlying 46 the epidemicity are poorly understood and remain under debate [6], robust toxin production 47 and sporulation [7], altered surface properties [8], resistance to antimicrobials [5, 9] and an 48 increased ability to metabolize certain sugars [10] have been implicated. 49In other organisms, the contribution of plasmid-encoded functions to virulence and 50 pathogenesis is well-documented [11][12][13]. By contrast, only a limited number of plasmids has 51 been identified in C. difficile and all of these are cryptic, i.e. no traits have been associated 52 with plasmid carriage. Commonly used cloning vectors for C. difficile make use of a replicon 53 derived from the 6.8 kb plasmid pCD6 [14]. The reference strain 630 contains a single 54 plasmid, pCD630, that is part of a larger family of 7.8-11.8 kb plasmids [15, 16]. And recently 55 several large (>42 kb) plasmids were described [17]. Neverthele...

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BAGEL4: a user-friendly web server to thoroughly mine RiPPs and bacteriocins

Cited by 708 publications

References 19 publications

Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family

Precursor peptide-targeted mining of more than one hundred thousand genomes expands the lanthipeptide natural product family

Cold‐adapted Bacilli isolated from the Qinghai–Tibetan Plateau are able to promote plant growth in extreme environments

Anin silicosurvey ofClostridioides difficileextrachromosomal elements

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