Bacterial diversity and chemical ecology of natural product–producing bacteria from Great Salt Lake sediment
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PROVIDER: S-EPMC10960970 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Great Salt Lake (GSL), located northwest of Salt Lake City, UT, is the largest terminal lake in the United States. While the average salinity of seawater is ~3.3%, the salinity in GSL ranges between 5-28%. In addition to being a hypersaline environment, GSL also contains toxic concentrations of heavy metals, such as arsenic, mercury, and lead. The extreme environment of GSL makes it an intriguing subject of study, both for its unique microbiome and its potential to harbor novel natural product-producing bacteria, which could be used as resources for the discovery of biologically active compounds. Though work has been done to survey and catalogue bacteria found in GSL, the Lake's microbiome is largely unexplored, and little-to-no work has been done to characterize the natural product potential of GSL microbes. Here, we investigate the bacterial diversity of two important regions within GSL, describe the first genomic characterization of Actinomycetota isolated from GSL sediment, including the identification of a new Saccharomonospora species, and provide the first survey of the natural product potential of GSL bacteria.
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Project description:Environmental microorganisms continue to serve as a major source of bioactive natural products (NPs) and as an inspiration for many other scaffolds in the toolbox of modern medicine. Nearly all microbial NP-inspired therapies can be traced to field expeditions to collect samples from the environment. Despite the importance of these expeditions in the search for new drugs, few studies have attempted to document the extent to which NPs or their corresponding production genes are distributed within a given environment. To gain insights into this, the geographic occurrence of NP ketosynthase (KS) and adenylation (A) domains was documented across 53 and 58 surface sediment samples, respectively, covering 59,590 square kilometers of Lake Huron. Overall, no discernible NP geographic distribution patterns were observed for 90,528 NP classes of nonribosomal peptides and polyketides detected in the survey. While each sampling location harbored a similar number of A domain operational biosynthetic units (OBUs), a limited overlap of OBU type was observed, suggesting that at the sequencing depth used in this study, no single location served as a NP "hotspot". These data support the hypothesis that there is ample variation in NP occurrence between sampling sites and suggest that extensive sample collection efforts are required to fully capture the functional chemical diversity of sediment microbial communities on a regional scale.
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Project description:Viruses play vital biogeochemical and ecological roles by (a) expressing auxiliary metabolic genes during infection, (b) enhancing the lateral transfer of host genes, and (c) inducing host mortality. Even in harsh and extreme environments, viruses are major players in carbon and nutrient recycling from organic matter. However, there is much that we do not yet understand about viruses and the processes mediated by them in the extreme environments such as hypersaline habitats. The Great Salt Lake (GSL) in Utah, United States is a hypersaline ecosystem where the biogeochemical role of viruses is poorly understood. This study elucidates the diversity of viruses and describes virus-host interactions in GSL sediments along a salinity gradient. The GSL sediment virosphere consisted of Haloviruses (32.07 ± 19.33%) and members of families Siphoviridae (39.12 ± 19.8%), Myoviridae (13.7 ± 6.6%), and Podoviridae (5.43 ± 0.64%). Our results demonstrate that salinity alongside the concentration of organic carbon and inorganic nutrients (nitrogen and phosphorus) governs the viral, bacteria, and archaeal diversity in this habitat. Computational host predictions for the GSL viruses revealed a wide host range with a dominance of viruses that infect Proteobacteria, Actinobacteria, and Firmicutes. Identification of auxiliary metabolic genes for photosynthesis (psbA), carbon fixation (rbcL, cbbL), formaldehyde assimilation (SHMT), and nitric oxide reduction (NorQ) shed light on the roles played by GSL viruses in biogeochemical cycles of global relevance.
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Project description:Seasonal changes in the microbial community in sediments of two carbonate-factory lakes (raw sequence reads)
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Project description:Streptomyces sp. GSL-6B was isolated from sediment collected from the Great Salt Lake and investigation of its organic extract led to the isolation of three new linear heptapeptides, bonnevillamides A (1), B (2), and C (3). The bonnevillamides represent a new class of linear peptides featuring unprecedented non-proteinogenic amino acids. All three peptides contain the newly characterized bonnevillic acid moiety (3-(3,5-dichloro-4-methoxyphenyl)-2-hydroxyacrylic acid), as well as a heavily modified proline residue. Moreover, in bonnevillamide A, the terminal proline residue found in bonnevillamides B and C is replaced with 4-methyl-azetidine-2-carboxylic acid methyl ester. The structures of the three heptapeptides were elucidated by NMR, high-resolution electrospray ionization mass spectroscopy (HRESIMS), and LC-MS/MS, and the absolute configuration of all proteinogenic amino acid residues were determined by advanced Marfey's method. Bonnevillamides A, B and C were evaluated for their effects on zebrafish embryo development. All three heptapeptides were shown to modulate heart growth and cardiac function, with bonnevillamide B having the most pronounced effect.
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Project description:Natural products are the result of Nature's exploration of biologically relevant chemical space through evolution and an invaluable source of bioactive small molecules for chemical biology and medicinal chemistry. Novel concepts for the discovery of new bioactive compound classes based on natural product structure may enable exploration of wider biologically relevant chemical space. The pseudo-natural product concept merges the relevance of natural product structure with efficient exploration of chemical space by means of fragment-based compound development to inspire the discovery of new bioactive chemical matter through de novo combination of natural product fragments in unprecedented arrangements. The novel scaffolds retain the biological relevance of natural products but are not obtainable through known biosynthetic pathways which can lead to new chemotypes that may have unexpected or unprecedented bioactivities. Herein, we cover the workflow of pseudo-natural product design and development, highlight recent examples, and discuss a cheminformatic analysis in which a significant portion of biologically active synthetic compounds were found to be pseudo-natural products. We compare the concept to natural evolution and discuss pseudo-natural products as the human-made equivalent, i.e. the chemical evolution of natural product structure.
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Project description:RNA from Lake Michigan sediment was hybridized with a DNA probe for archaeal 16S rRNA. There was a peak of archaeal rRNA abundance in the oxic zone and another immediately below it. Six contributing species were identified by PCR amplification of extracted DNA with primers specific for archaeal rDNA: two related to Methanosarcina acetivorans and four related to marine crenarchaeotal sequences. rRNA quantification using a DNA probe specific for this crenarchaeotal assemblage showed it is most abundant in the oxic zone, where it accounts for about 10% of total archaeal rRNA.
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Project description:Pseudo-natural products (PNPs) combine natural product (NP) fragments in novel arrangements not accessible by current biosynthesis pathways. As such they can be regarded as non-biogenic fusions of NP-derived fragments. They inherit key biological characteristics of the guiding natural product, such as chemical and physiological properties, yet define small molecule chemotypes with unprecedented or unexpected bioactivity. We iterate the design principles underpinning PNP scaffolds and highlight their syntheses and biological investigations. We provide a cheminformatic analysis of PNP collections assessing their molecular properties and shape diversity. We propose and discuss how the iterative analysis of NP structure, design, synthesis, and biological evaluation of PNPs can be regarded as a human-driven branch of the evolution of natural products, that is, a chemical evolution of natural product structure.
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Project description:Halophiles are relatively unexplored as potential sources of novel species. However, little is known about the culturable bacterial diversity thrive in hypersaline lakes. In this work, a total of 343 bacteria from sediment samples of Aiding Lake, China, were isolated using nine different media supplemented with 5% or 15% (w/v) NaCl. The number of species and genera of bacteria recovered from the different media varied, indicating the need to optimize the isolation conditions. The results showed an unexpected level of bacterial diversity, with four phyla (Actinobacteria, Firmicutes, Proteobacteria, and Rhodothermaeota), fourteen orders (Actinopolysporales, Alteromonadales, Bacillales, Balneolales, Chromatiales, Glycomycetales, Jiangellales, Micrococcales, Micromonosporales, Oceanospirillales, Pseudonocardiales, Rhizobiales, Streptomycetales, and Streptosporangiales), including 17 families, 43 genera (including two novel genera), and 71 species (including four novel species). The predominant phyla included Actinobacteria and Firmicutes and the predominant genera included Actinopolyspora, Gracilibacillus, Halomonas, Nocardiopsis, and Streptomyces. To our knowledge, this is the first time that members of phylum Rhodothermaeota were identified in sediment samples from a salt lake.
| S-EPMC7351256 | biostudies-literature