scholarly journals Bacterial secondary metabolite biosynthetic potential in soil varies with phylum, depth, and vegetation type

2019 ◽  
Author(s):  
Allison M. Sharrar ◽  
Alexander Crits-Christoph ◽  
Raphaël Méheust ◽  
Spencer Diamond ◽  
Evan P. Starr ◽  
...  

AbstractBacteria isolated from soils are major sources of specialized metabolites, including antibiotics and other compounds with clinical value that likely shape interactions among microbial community members and impact biogeochemical cycles. Yet, isolated lineages represent a small fraction of all soil bacterial diversity. It remains unclear how the production of specialized metabolites varies across the phylogenetic diversity of bacterial species in soils, and whether the genetic potential for production of these metabolites differs with soil type. We sampled soils and saprolite from three sites in a northern California Critical Zone Observatory with varying vegetation and bedrock characteristics and used metagenomic sequencing and assembly to reconstruct 1,334 microbial genomes containing diverse biosynthetic gene clusters (BGCs) for secondary metabolite production. We obtained genomes for prolific producers of secondary metabolites, including novel groups within the Actinobacteria, Chloroflexi and candidate phylum Dormibactereota. Surprisingly, one genome of a Candidate Phyla Radiation bacterium encoded for a ribosomally synthesized linear azole/azoline-containing peptide, a capacity we found in other publicly available CPR bacterial genomes. Overall, bacteria with higher biosynthetic potential were enriched in shallow soils and grassland soils, with patterns of abundance of BGC type varying by taxonomy.

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Allison M. Sharrar ◽  
Alexander Crits-Christoph ◽  
Raphaël Méheust ◽  
Spencer Diamond ◽  
Evan P. Starr ◽  
...  

ABSTRACT Bacteria isolated from soils are major sources of specialized metabolites, including antibiotics and other compounds with clinical value that likely shape interactions among microbial community members and impact biogeochemical cycles. Yet, isolated lineages represent a small fraction of all soil bacterial diversity. It remains unclear how the production of specialized metabolites varies across the phylogenetic diversity of bacterial species in soils and whether the genetic potential for production of these metabolites differs with soil depth and vegetation type within a geographic region. We sampled soils and saprolite from three sites in a northern California Critical Zone Observatory with various vegetation and bedrock characteristics and reconstructed 1,334 metagenome-assembled genomes containing diverse biosynthetic gene clusters (BGCs) for secondary metabolite production. We obtained genomes for prolific producers of secondary metabolites, including novel groups within the Actinobacteria, Chloroflexi, and candidate phylum “Candidatus Dormibacteraeota.” Surprisingly, one genome of a candidate phyla radiation (CPR) bacterium coded for a ribosomally synthesized linear azole/azoline-containing peptide, a capacity we found in other publicly available CPR bacterial genomes. Overall, bacteria with higher biosynthetic potential were enriched in shallow soils and grassland soils, with patterns of abundance of BGC type varying by taxonomy. IMPORTANCE Microbes produce specialized compounds to compete or communicate with one another and their environment. Some of these compounds, such as antibiotics, are also useful in medicine and biotechnology. Historically, most antibiotics have come from soil bacteria which can be isolated and grown in the lab. Though the vast majority of soil bacteria cannot be isolated, we can extract their genetic information and search it for genes which produce these specialized compounds. These understudied soil bacteria offer a wealth of potential for the discovery of new and important microbial products. Here, we identified the ability to produce these specialized compounds in diverse and novel bacteria in a range of soil environments. This information will be useful to other researchers who wish to isolate certain products. Beyond their use to humans, understanding the distribution and function of microbial products is key to understanding microbial communities and their effects on biogeochemical cycles.


2020 ◽  
Author(s):  
Mathew Storey ◽  
SK Andreassend ◽  
Joe Bracegirdle ◽  
Alistair Brown ◽  
Robert Keyzers ◽  
...  

© 2020 Storey et al. Marine sponges have been a prolific source of unique bioactive compounds that are presumed to act as a deterrent to predation. Many of these compounds have potential therapeutic applications; however, the lack of efficient and sustainable synthetic routes frequently limits clinical development. Here, we describe a metag-enomic investigation of Mycale hentscheli, a chemically gifted marine sponge that pos-sesses multiple distinct chemotypes. We applied shotgun metagenomic sequencing, hybrid assembly of short-and long-read data, and metagenomic binning to obtain a comprehensive picture of the microbiome of five specimens, spanning three chemo-types. Our data revealed multiple producing species, each having relatively modest secondary metabolomes, that contribute collectively to the chemical arsenal of the holo-biont. We assembled complete genomes for multiple new genera, including two species that produce the cytotoxic polyketides pateamine and mycalamide, as well as a third high-abundance symbiont harboring a proteusin-type biosynthetic pathway that appears to encode a new polytheonamide-like compound. We also identified an additional 188 biosynthetic gene clusters, including a pathway for biosynthesis of peloruside. These re-sults suggest that multiple species cooperatively contribute to defensive symbiosis in M. hentscheli and reveal that the taxonomic diversity of secondary-metabolite-producing sponge symbionts is larger and richer than previously recognized. IMPORTANCE Mycale hentscheli is a marine sponge that is rich in bioactive small mol-ecules. Here, we use direct metagenomic sequencing to elucidate highly complete and contiguous genomes for the major symbiotic bacteria of this sponge. We identify complete biosynthetic pathways for the three potent cytotoxic polyketides which have previously been isolated from M. hentscheli. Remarkably, and in contrast to previous studies of marine sponges, we attribute each of these metabolites to a different producing mi-crobe. We also find that the microbiome of M. hentscheli is stably maintained among in-dividuals, even over long periods of time. Collectively, our data suggest a cooperative mode of defensive symbiosis in which multiple symbiotic bacterial species cooperatively contribute to the defensive chemical arsenal of the holobiont.


mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Mathew A. Storey ◽  
Sarah K. Andreassend ◽  
Joe Bracegirdle ◽  
Alistair Brown ◽  
Robert A. Keyzers ◽  
...  

ABSTRACT Marine sponges have been a prolific source of unique bioactive compounds that are presumed to act as a deterrent to predation. Many of these compounds have potential therapeutic applications; however, the lack of efficient and sustainable synthetic routes frequently limits clinical development. Here, we describe a metagenomic investigation of Mycale hentscheli, a chemically gifted marine sponge that possesses multiple distinct chemotypes. We applied shotgun metagenomic sequencing, hybrid assembly of short- and long-read data, and metagenomic binning to obtain a comprehensive picture of the microbiome of five specimens, spanning three chemotypes. Our data revealed multiple producing species, each having relatively modest secondary metabolomes, that contribute collectively to the chemical arsenal of the holobiont. We assembled complete genomes for multiple new genera, including two species that produce the cytotoxic polyketides pateamine and mycalamide, as well as a third high-abundance symbiont harboring a proteusin-type biosynthetic pathway that appears to encode a new polytheonamide-like compound. We also identified an additional 188 biosynthetic gene clusters, including a pathway for biosynthesis of peloruside. These results suggest that multiple species cooperatively contribute to defensive symbiosis in M. hentscheli and reveal that the taxonomic diversity of secondary-metabolite-producing sponge symbionts is larger and richer than previously recognized. IMPORTANCE Mycale hentscheli is a marine sponge that is rich in bioactive small molecules. Here, we use direct metagenomic sequencing to elucidate highly complete and contiguous genomes for the major symbiotic bacteria of this sponge. We identify complete biosynthetic pathways for the three potent cytotoxic polyketides which have previously been isolated from M. hentscheli. Remarkably, and in contrast to previous studies of marine sponges, we attribute each of these metabolites to a different producing microbe. We also find that the microbiome of M. hentscheli is stably maintained among individuals, even over long periods of time. Collectively, our data suggest a cooperative mode of defensive symbiosis in which multiple symbiotic bacterial species cooperatively contribute to the defensive chemical arsenal of the holobiont.


2020 ◽  
Author(s):  
Mathew Storey ◽  
SK Andreassend ◽  
Joe Bracegirdle ◽  
Alistair Brown ◽  
Robert Keyzers ◽  
...  

© 2020 Storey et al. Marine sponges have been a prolific source of unique bioactive compounds that are presumed to act as a deterrent to predation. Many of these compounds have potential therapeutic applications; however, the lack of efficient and sustainable synthetic routes frequently limits clinical development. Here, we describe a metag-enomic investigation of Mycale hentscheli, a chemically gifted marine sponge that pos-sesses multiple distinct chemotypes. We applied shotgun metagenomic sequencing, hybrid assembly of short-and long-read data, and metagenomic binning to obtain a comprehensive picture of the microbiome of five specimens, spanning three chemo-types. Our data revealed multiple producing species, each having relatively modest secondary metabolomes, that contribute collectively to the chemical arsenal of the holo-biont. We assembled complete genomes for multiple new genera, including two species that produce the cytotoxic polyketides pateamine and mycalamide, as well as a third high-abundance symbiont harboring a proteusin-type biosynthetic pathway that appears to encode a new polytheonamide-like compound. We also identified an additional 188 biosynthetic gene clusters, including a pathway for biosynthesis of peloruside. These re-sults suggest that multiple species cooperatively contribute to defensive symbiosis in M. hentscheli and reveal that the taxonomic diversity of secondary-metabolite-producing sponge symbionts is larger and richer than previously recognized. IMPORTANCE Mycale hentscheli is a marine sponge that is rich in bioactive small mol-ecules. Here, we use direct metagenomic sequencing to elucidate highly complete and contiguous genomes for the major symbiotic bacteria of this sponge. We identify complete biosynthetic pathways for the three potent cytotoxic polyketides which have previously been isolated from M. hentscheli. Remarkably, and in contrast to previous studies of marine sponges, we attribute each of these metabolites to a different producing mi-crobe. We also find that the microbiome of M. hentscheli is stably maintained among in-dividuals, even over long periods of time. Collectively, our data suggest a cooperative mode of defensive symbiosis in which multiple symbiotic bacterial species cooperatively contribute to the defensive chemical arsenal of the holobiont.


2019 ◽  
Author(s):  
Wenfa Ng

Actinobacteria and streptomyces are known to produce a variety of natural products, some of which confer antibiotic or immunosuppressive activities. While it is understandable that microbes develop the ability to synthesize molecules such as antibiotics that attack other competing microbes, but why would a secondary metabolite (natural product) synthesized by a microbe confer immunosuppressive activities? Was the capability to synthesize such a molecule endowed by evolution in the context of enabling microbes to develop resistance to immune cells of the human body? Or did the capability come from the need to colonize human body surfaces or gut to gain a survival niche for the microbe? Given that actinobacteria and streptomyces are soil microbes not usually associated with human body surfaces, could their biosynthetic capability for particular immunosuppressants arise from horizontal gene transfer from bacteria that colonize human body surfaces and subsequently develop the ability to synthesize the pertinent compounds through evolution? An alternate line of thinking on this issue touches on the possibility that microbes could encounter analogs of immuno-active molecules in their natural environment. Such molecules might elicit undesired physiological effects on the microbes, which place a selection pressure on microbes to develop countermeasures to the immuno-active molecules through mutations. Hence, through evolution, microbes could have developed the capability to synthesize secondary metabolites able to bind analogs of immuno-active molecules and help sequester them or quench their bioactivity. Subsequent profiling of such secondary metabolites in drug discovery efforts could have uncovered compounds with immunosuppressant activity which are originally developed for counteracting analogs of immuno-active molecules in the environment. It has to be recognized that analogs of immuno-active compounds remain somewhat dissimilar to immune compounds secreted by human immune cells, but they likely share common motifs for protein-secondary metabolite interactions. Direct evidence of the evolution of natural products with immunosuppressant activities could only be obtained from challenging suitable bacterial species with immuno-active molecules. Long cultivation experiments with multiple generations may result in the evolution of biosynthetic gene clusters for the synthesis of natural products able to sequester or quench immuno-active molecules. But, on the another hand, understanding relative binding affinities between a library of natural products and immuno-active molecules from humans would suggest drug candidates and their biosynthetic gene clusters. Subsequent phylogenetic analysis of cluster genes with their homologs from other species may yield insights into the evolution of genes and their putative function.


2021 ◽  
Author(s):  
Xinzhao Tong ◽  
Marcus H. Y. Leung ◽  
Zhiyong Shen ◽  
Justin Y. Y. Lee ◽  
Christopher E. Mason ◽  
...  

Abstract Background: Studies of the microbiomes on surfaces in built environment have largely focused on indoor spaces, while outdoor spaces have received far less attention. Piers are engineered infrastructures commonly found in coastal areas, and due to their unique locations at the interface between terrestrial and aquatic ecosystems, pier surfaces are likely to harbor interesting microbiology. In this study, the microbiomes on the metal and concrete surfaces at nine piers located along the coastline of Hong Kong were investigated by metagenomic sequencing. The roles played by different factors in shaping the taxonomic composition and functional traits of the pier surface microbiomes were determined. Metagenome-assembled genomes were reconstructed and their putative biosynthetic gene clusters were characterized in detail.Results: Surface material was found to be the strongest factor in structuring the taxonomic and functional compositions of the pier surface microbiomes. Corrosion-related bacteria were significantly enriched on metal surfaces, consistent with the pitting corrosion observed. The differential enrichment of taxa mediating biodegradation suggests differences between the metal and concrete surfaces in terms of specific xenobiotics being potentially degraded. Genome-centric analysis detected the presence of many novel species, with the majority of them belonging to the phylum Proteobacteria. Genomic characterization showed that the potential metabolic functions and secondary biosynthetic capacity were largely governed by taxonomy, rather than surface attributes and geography. Conclusions: Pier surfaces are a rich reservoir of abundant novel bacterial species. Members of the surface microbial communities use different mechanisms to counter the stresses under oligotrophic conditions. A better understanding of the outdoor surface microbiomes located in different environments should enhance the ability to maintain outdoor surfaces of infrastructures.


2019 ◽  
Author(s):  
Wenfa Ng

Actinobacteria and streptomyces are known to produce a variety of natural products, some of which confer antibiotic or immunosuppressive activities. While it is understandable that microbes develop the ability to synthesize molecules such as antibiotics that attack other competing microbes, but why would a secondary metabolite (natural product) synthesized by a microbe confer immunosuppressive activities? Was the capability to synthesize such a molecule endowed by evolution in the context of enabling microbes to develop resistance to immune cells of the human body? Or did the capability come from the need to colonize human body surfaces or gut to gain a survival niche for the microbe? Given that actinobacteria and streptomyces are soil microbes not usually associated with human body surfaces, could their biosynthetic capability for particular immunosuppressants arise from horizontal gene transfer from bacteria that colonize human body surfaces and subsequently develop the ability to synthesize the pertinent compounds through evolution? An alternate line of thinking on this issue touches on the possibility that microbes could encounter analogs of immuno-active molecules in their natural environment. Such molecules might elicit undesired physiological effects on the microbes, which place a selection pressure on microbes to develop countermeasures to the immuno-active molecules through mutations. Hence, through evolution, microbes could have developed the capability to synthesize secondary metabolites able to bind analogs of immuno-active molecules and help sequester them or quench their bioactivity. Subsequent profiling of such secondary metabolites in drug discovery efforts could have uncovered compounds with immunosuppressant activity which are originally developed for counteracting analogs of immuno-active molecules in the environment. It has to be recognized that analogs of immuno-active compounds remain somewhat dissimilar to immune compounds secreted by human immune cells, but they likely share common motifs for protein-secondary metabolite interactions. Direct evidence of the evolution of natural products with immunosuppressant activities could only be obtained from challenging suitable bacterial species with immuno-active molecules. Long cultivation experiments with multiple generations may result in the evolution of biosynthetic gene clusters for the synthesis of natural products able to sequester or quench immuno-active molecules. But, on the another hand, understanding relative binding affinities between a library of natural products and immuno-active molecules from humans would suggest drug candidates and their biosynthetic gene clusters. Subsequent phylogenetic analysis of cluster genes with their homologs from other species may yield insights into the evolution of genes and their putative function.


Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Xinzhao Tong ◽  
Marcus H. Y. Leung ◽  
Zhiyong Shen ◽  
Justin Y. Y. Lee ◽  
Christopher E. Mason ◽  
...  

Abstract Background Studies of the microbiomes on surfaces in built environment have largely focused on indoor spaces, while outdoor spaces have received far less attention. Piers are engineered infrastructures commonly found in coastal areas, and due to their unique locations at the interface between terrestrial and aquatic ecosystems, pier surfaces are likely to harbor interesting microbiology. In this study, the microbiomes on the metal and concrete surfaces at nine piers located along the coastline of Hong Kong were investigated by metagenomic sequencing. The roles played by different physical attributes and environmental factors in shaping the taxonomic composition and functional traits of the pier surface microbiomes were determined. Metagenome-assembled genomes were reconstructed and their putative biosynthetic gene clusters were characterized in detail. Results Surface material was found to be the strongest factor in structuring the taxonomic and functional compositions of the pier surface microbiomes. Corrosion-related bacteria were significantly enriched on metal surfaces, consistent with the pitting corrosion observed. The differential enrichment of taxa mediating biodegradation suggests differences between the metal and concrete surfaces in terms of specific xenobiotics being potentially degraded. Genome-centric analysis detected the presence of many novel species, with the majority of them belonging to the phylum Proteobacteria. Genomic characterization showed that the potential metabolic functions and secondary biosynthetic capacity were largely correlated with taxonomy, rather than surface attributes and geography. Conclusions Pier surfaces are a rich reservoir of abundant novel bacterial species. Members of the surface microbial communities use different mechanisms to counter the stresses under oligotrophic conditions. A better understanding of the outdoor surface microbiomes located in different environments should enhance the ability to maintain outdoor surfaces of infrastructures.


2021 ◽  
pp. 2620-2624
Author(s):  
Wilis Ari Setyati ◽  
Delianis Pringgenies ◽  
Nirwani Soenardjo ◽  
Rini Pramesti

Background and Aim: Actinomycetes are a group of Gram-positive bacteria with a fungus-like morphology. Their natural habitat encompasses terrestrial and water areas, including mangrove ecosystems. This study aimed to assess the PKS and NRPS genes as the producers of secondary metabolites and to determine the target bacterial species using molecular DNA tests. Materials and Methods: In this study, we isolated bacteria from sediment samples from mangrove forests located on Karimunjawa Islands and in Semarang city, purified bacteria, screened for antibacterial activity, extracted bacterial DNA, amplified the NRPS gene, detected and amplified the PKS-I and PKS-II genes, amplified and sequenced the 16S rRNA, processed molecular data, and simulated a map of secondary metabolite producing genes. Results: Samples from the Karimunjawa Islands yielded 19 bacterial isolates, whereas samples from Semarang yielded 11 bacterial isolates after culture in different media. Further experiments identified three active isolates, which were termed PN.SB.6.2, S.SK.6.3, and S.SK.7.1, against pathogenic species of Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes. Isolate PN.SB.6.2 was determined to possess three biosynthetic gene clusters (BGCs), whereas the remaining two isolates, S.SK.6.3 and S.SK.7.1, only possessed two BGCs, namely, NRPS and PKS II. Conclusion: Products were estimated to be in the NRPS, thiopeptide, RiPP-like, siderophore, betalactone, terpene, Type III PKS, CDPS, and lassopeptide groups. DNA identification of the isolates found three species of actinomycetes with antibacterial potential, namely, Virgibacillus salaries, Bacillus licheniformis, and Priestia flexa.


2021 ◽  
Author(s):  
Alexander Crits-Christoph ◽  
Spencer Diamond ◽  
Basem Al-Shayeb ◽  
Luis Valentin-Alvarado ◽  
Jillian F Banfield

Bacteria of the phylum Acidobacteria are one of the most abundant bacterial across soil ecosystems, yet they are represented by comparatively few sequenced genomes, leaving gaps in our understanding of their metabolic diversity. Recently, genomes of Acidobacteria species with unusually large repertoires of biosynthetic gene clusters (BGCs) were reconstructed from grassland soil metagenomes, but the degree to which these species are widespread is still unknown. To investigate this, we augmented a dataset of publicly available Acidobacteria genomes with 46 metagenome-assembled genomes recovered from permanently saturated organic-rich soils of a vernal (spring) pool ecosystem in Northern California. We recovered high quality genomes for three novel species from Candidatus Angelobacter (a proposed subdivision 1 Acidobacterial genus), a genus that is genomically enriched in genes for specialized metabolite biosynthesis. Acidobacteria were particularly abundant in the vernal pool sediments, and a Ca. Angelobacter species was the most abundant bacterial species detected in some samples. We identified numerous diverse biosynthetic gene clusters in these genomes, and also in additional genomes from other publicly available soil metagenomes for other related Ca. Angelobacter species. Metabolic analysis indicates that Ca. Angelobacter likely are aerobes that ferment organic carbon, with potential to contribute to carbon compound turnover in soils. Using metatranscriptomics, we identified in situ expression of specialized metabolic traits for two species from this genus. In conclusion, we expand genomic sampling of the uncultivated Ca. Angelobacter, and show that they represent common and sometimes highly abundant members of dry and saturated soil communities, with a high degree of capacity for synthesis of diverse specialized metabolites.


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