scholarly journals Absynte: a web tool to analyze the evolution of orthologous archaeal and bacterial gene clusters

2011 ◽  
Vol 27 (20) ◽  
pp. 2905-2906 ◽  
Author(s):  
A. Despalins ◽  
S. Marsit ◽  
J. Oberto
Keyword(s):  
Gene Clusters ◽  
Web Tool ◽  
Bacterial Gene

scholarly journals A widespread family of bacterial gene clusters produces ClpP inhibitors

2021 ◽  
Author(s):  
Gerry Wright ◽  
Elizabeth Culp ◽  
David Sychantha ◽  
Christian Hobson ◽  
Andrew Pawlowski ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Genome Mining ◽  
Antibiotic Resistance Genes ◽  
Gene Clusters ◽  
Biosynthetic Gene Clusters ◽  
Bacterial Gene ◽  
Clinical Potential ◽  
Novel Scaffold

Abstract Intracellular proteolytic complexes play an essential role in modeling the proteome in both bacteria and eukaryotes. ClpP is the protease subunit of one such highly conserved proteolytic complex that, despite its potential, remains unexploited as a drug target. Here we describe a target-directed genome mining strategy to identify ClpP targeting compounds from the bacterial order Actinomycetales. By searching for biosynthetic gene clusters that contain duplicated copies of ClpP as putative antibiotic resistance genes, we identify a family of ClpP-associated clusters that are widespread across phyla, including environmental and pathogenic bacteria. While numerous bacterial pyrrolizidine alkaloids produced by these gene clusters are known, their connection to ClpP has never been made. We show that these previously characterized molecules do not affect ClpP function but are shunt metabolites derived from the genuine product of these gene clusters, a reactive covalent ClpP inhibitor. Focusing on one such cryptic gene cluster from Streptomyces cattleya DSM 46488, we use heterologous expression to purify the relevant ClpP inhibitor, which we name clipibicyclene. We show in vitro and in vivo that clipibicyclene is a potent covalent inhibitor of ClpP and that cluster-associated ClpPs provide resistance. ClpP inhibition results in antibacterial activity against actinobacteria, including Mycobacterium smegmatis, and inhibition of virulence factor production by Staphylococcus aureus. Finally, we solve the crystal structure of clipibicyclene-modified Escherichia coli ClpP. Clipibicyclene’s discovery deconvolutes the actual function of a family of natural products widespread in nature. It provides a novel scaffold for therapeutic ClpP inhibitor development, making these findings significant from the perspective of their discovery and their clinical potential.

scholarly journals Massive Gene Flux Drives Genome Diversity between Sympatric Streptomyces Conspecifics

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Abdoul-Razak Tidjani ◽  
Jean-Noël Lorenzi ◽  
Maxime Toussaint ◽  
Erwin van Dijk ◽  
Delphine Naquin ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Public Goods ◽  
Significant Proportion ◽  
Gene Clusters ◽  
Recent Common Ancestor ◽  
Natural Soil ◽  
Gene Pools ◽  
Bacterial Gene ◽  
Integrative And Conjugative Elements

ABSTRACT In this work, by comparing genomes of closely related individuals of Streptomyces isolated at a spatial microscale (millimeters or centimeters), we investigated the extent and impact of horizontal gene transfer in the diversification of a natural Streptomyces population. We show that despite these conspecific strains sharing a recent common ancestor, all harbored significantly different gene contents, implying massive and rapid gene flux. The accessory genome of the strains was distributed across insertion/deletion events (indels) ranging from one to several hundreds of genes. Indels were preferentially located in the arms of the linear chromosomes (ca. 12 Mb) and appeared to form recombination hot spots. Some of them harbored biosynthetic gene clusters (BGCs) whose products confer an inhibitory capacity and may constitute public goods that can favor the cohesiveness of the bacterial population. Moreover, a significant proportion of these variable genes were either plasmid borne or harbored signatures of actinomycete integrative and conjugative elements (AICEs). We propose that conjugation is the main driver for the indel flux and diversity in Streptomyces populations. IMPORTANCE Horizontal gene transfer is a rapid and efficient way to diversify bacterial gene pools. Currently, little is known about this gene flux within natural soil populations. Using comparative genomics of Streptomyces strains belonging to the same species and isolated at microscale, we reveal frequent transfer of a significant fraction of the pangenome. We show that it occurs at a time scale enabling the population to diversify and to cope with its changing environment, notably, through the production of public goods.

scholarly journals Computational modelling of Chromosomally Clustering Protein Domains In Bacteria

2021 ◽  
Author(s):  
Chiara E. Cotroneo ◽  
Isobel Claire Gormley ◽  
Denis C. Shields ◽  
Michael Salter-Townshend
Keyword(s):  
Gene Ontology ◽  
Mixture Model ◽  
Computational Modelling ◽  
Protein Domains ◽  
Gene Clusters ◽  
Protein Domain ◽  
Parameter Estimates ◽  
Bacterial Gene ◽  
Wide Range ◽  
The Stability

Abstract Background: In bacteria, genes with related functions - such as those involved in the metabolism of the same compound or in infection processes - are often physically close on the genome and form groups called clusters. The enrichment of such clusters over various distantly related bacteria can be used to predict the roles of genes of unknown function that cluster with characterised genes. There is no obvious rule to define a cluster, given their variability in size and intergenic distances, and the definition of what comprises a “gene”, since genes can gain and lose domains over time. Protein domains can cluster within a gene, or in adjacent genes of related function, and in both cases these are chromosomally clustered. Here, we model the distances between pairs of protein domain coding regions across a wide range of bacteria and archaea via a probabilistic two component mixture model, without imposing arbitrary thresholds in terms of gene numbers or distances. Results: We trained our model using matched Gene Ontology terms to label functionally related pairs and assess the stability of the parameters of the model across 14, 178 archaeal and bacterial strains. We found that the parameters of our mixture model are remarkably stable across bacteria and archaea, except for endosymbionts and obligate intracellular pathogens. Obligate pathogens have smaller genomes, and although they vary, on average do not show noticeably different clustering distances; the main difference in the parameter estimates is that a far greater proportion of the genes sharing ontology terms are clustered. This may reflect that these genomes are enriched for complexes encoded by clustered core housekeeping genes, as a proportion of the total genes. Given the overall stability of the parameter estimates, we then used the mean parameter estimates across the entire dataset to investigate which gene ontology terms are most frequently associated with clustered genes. Conclusions: Given the stability of the mixture model across species, it may be used to predict bacterial gene clusters that are shared across multiple species, in addition to giving insights into the evolutionary pressures on the chromosomal locations of genes in different species.

scholarly journals Sift-PULs: A public repository for specific functional polysaccharide utilization loci

2021 ◽  
Author(s):  
Tao Song ◽  
Congchong Wei ◽  
Dezhi Yuan ◽  
Shengwei Xiang ◽  
Lin Liu ◽  
...  
Keyword(s):  
Biochemical Characterization ◽  
Gene Clusters ◽  
Public Repository ◽  
Function Annotation ◽  
Bacterial Gene ◽  
Bacterial Phyla ◽  
Signature Genes ◽  
Specific Polysaccharide ◽  
Encoding Genes ◽  
Polysaccharide Utilization Loci

Background Polysaccharide utilization loci (PULs) were bacterial gene clusters encoding genes responsible for polysaccharide utilization process. PUL studies are blooming in recent years but the biochemical characterization speed is relative slow. There is a growing demand for PUL database with function annotations. Results Using signature genes corresponding for specific polysaccharide, 10422 PULs specific for 6 polysaccharides (agar, alginate, pectin, carrageenan, chitin and β-manan) from various bacterial phyla were predicted. Then online website of specific functional polysaccharide utilization loci (Sift-PULs) was constructed. Sift-PULs provides a repository where users could browse, search and download interested PULs without registration. Conclusions The key advantage of Sift-PULs is to assign a function annotation of each PUL, which is not available in existing PUL databases. PUL's functional annotation lays a foundation for studying novel enzymes, new pathways, PUL evolution or bioengineering. The website is available on http://sift-puls.org

scholarly journals Computational modelling of chromosomally clustering protein domains in bacteria

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chiara E. Cotroneo ◽  
Isobel Claire Gormley ◽  
Denis C. Shields ◽  
Michael Salter-Townshend
Keyword(s):  
Gene Ontology ◽  
Mixture Model ◽  
Computational Modelling ◽  
Protein Domains ◽  
Gene Clusters ◽  
Protein Domain ◽  
Parameter Estimates ◽  
Bacterial Gene ◽  
Wide Range ◽  
The Stability

Abstract Background In bacteria, genes with related functions—such as those involved in the metabolism of the same compound or in infection processes—are often physically close on the genome and form groups called clusters. The enrichment of such clusters over various distantly related bacteria can be used to predict the roles of genes of unknown function that cluster with characterised genes. There is no obvious rule to define a cluster, given their variability in size and intergenic distances, and the definition of what comprises a “gene”, since genes can gain and lose domains over time. Protein domains can cluster within a gene, or in adjacent genes of related function, and in both cases these are chromosomally clustered. Here, we model the distances between pairs of protein domain coding regions across a wide range of bacteria and archaea via a probabilistic two component mixture model, without imposing arbitrary thresholds in terms of gene numbers or distances. Results We trained our model using matched gene ontology terms to label functionally related pairs and assess the stability of the parameters of the model across 14,178 archaeal and bacterial strains. We found that the parameters of our mixture model are remarkably stable across bacteria and archaea, except for endosymbionts and obligate intracellular pathogens. Obligate pathogens have smaller genomes, and although they vary, on average do not show noticeably different clustering distances; the main difference in the parameter estimates is that a far greater proportion of the genes sharing ontology terms are clustered. This may reflect that these genomes are enriched for complexes encoded by clustered core housekeeping genes, as a proportion of the total genes. Given the overall stability of the parameter estimates, we then used the mean parameter estimates across the entire dataset to investigate which gene ontology terms are most frequently associated with clustered genes. Conclusions Given the stability of the mixture model across species, it may be used to predict bacterial gene clusters that are shared across multiple species, in addition to giving insights into the evolutionary pressures on the chromosomal locations of genes in different species.

scholarly journals (R)-1-hydroxy-2-aminoethylphosphonate ammonia-lyase, a new PLP-dependent enzyme involved in bacterial phosphonate degradation

2020 ◽  
Author(s):  
Erika Zangelmi ◽  
Toda Stankovic ◽  
Marco Malatesta ◽  
Domenico Acquotti ◽  
Katharina Pallitsch ◽  
...  
Keyword(s):  
Gene Clusters ◽  
Elimination Reaction ◽  
Stable Carbon ◽  
Bacterial Gene ◽  
Naturally Occurring ◽  
Number Of Microorganisms

Phosphonates contain a particularly stable carbon-phosphorus bond, yet a number of microorganisms possess pathways to degrade these molecules and use them as source of phosphorus. One example is the widespread hydrolytic route for the breakdown of 2-aminoethylphosphonate (AEP). In this pathway, the aminotransferase PhnW initially converts AEP into phosphonoacetaldehyde (PAA), which is then cleaved by the hydrolase PhnX to yield acetaldehyde and phosphate. This work focuses on a novel enzyme (hereby termed PbfA), which is often encoded in bacterial gene clusters containing the phnW-phnX combination. Although PbfA is annotated as a transaminase, we report that it catalyzes an elimination reaction on the naturally occurring compound (R)-1-hydroxy-2-aminoethylphosphonate (R-HAEP). The reaction releases ammonia and generates PAA, which can be subsequently hydrolyzed by PhnX. Overall, the PbfA reaction represents a frequent accessory branch in the hydrolytic pathway for AEP degradation, which expands the scope and versatility of the pathway itself.

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