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Organic & Biomolecular Chemistry Jun 2024Synthetic routes to geosmin and its enantiomer are well established, but the enantioselective synthesis of stereoisomers of geosmin is unknown. Here a stereoselective...
Synthetic routes to geosmin and its enantiomer are well established, but the enantioselective synthesis of stereoisomers of geosmin is unknown. Here a stereoselective synthesis of all stereoisomers of geosmin is reported, yielding all compounds in high enantiomeric purity. Furthermore, the stereoselective synthesis of a geosmin derivative isolated from a mangrove associated streptomycete was performed, establishing the absolute configuration of the natural product. Finally, a new side product of the geosmin synthase from was isolated and its structure was elucidated by NMR spectroscopy. The absolute configuration of this new compound was determined through a stereoselective synthesis.
PubMed: 38920404
DOI: 10.1039/d4ob00934g -
Journal of Agricultural and Food... Jun 2024Validamycin A (VMA) is an antifungal antibiotic derived from commonly used in plant disease management. Surprisingly, VMA was discovered to impede the production of...
Validamycin A (VMA) is an antifungal antibiotic derived from commonly used in plant disease management. Surprisingly, VMA was discovered to impede the production of fumonisin B1 (FB) in agricultural settings. However, the specific target of VMA in remained unclear. To unravel the molecular mechanism of VMA, ultrastructural observations unveiled damage to mitochondrial membranes. Trehalase (FvNth) was pinpointed as the target of VMA by utilizing a 3D-printed surface plasmon resonance sensor. Molecular docking identified Trp, Arg, Asp, and Phe as the binding sites between VMA and FvNth. A mutant lacking amino acids 250-670 was engineered through homologous recombination. Transcriptome analysis indicated that samples treated with VMA and displayed similar expression patterns, particularly in the suppression of the FUM gene cluster. VMA treatment resulted in reduced trehalase and ATPase activity as well as diminished production of glucose, pyruvic acid, and acetyl-CoA. Conversely, these effects were absent in samples treated with . This research proposes that VMA hinders acetyl-CoA synthesis by trehalase, thereby suppressing the FB biosynthesis. These findings present a novel target for the development of mycotoxin control agents.
PubMed: 38917402
DOI: 10.1021/acs.jafc.4c02641 -
NAR Genomics and Bioinformatics Jun 2024Microbial specialized metabolite biosynthetic gene clusters (SMBGCs) are a formidable source of natural products of pharmaceutical interest. With the multiplication of...
Microbial specialized metabolite biosynthetic gene clusters (SMBGCs) are a formidable source of natural products of pharmaceutical interest. With the multiplication of genomic data available, very efficient bioinformatic tools for automatic SMBGC detection have been developed. Nevertheless, most of these tools identify SMBGCs based on sequence similarity with enzymes typically involved in specialised metabolism and thus may miss SMBGCs coding for undercharacterised enzymes. Here we present Synteruptor (https://bioi2.i2bc.paris-saclay.fr/synteruptor), a program that identifies genomic islands, known to be enriched in SMBGCs, in the genomes of closely related species. With this tool, we identified a SMBGC in the genome of ATCC23877, undetected by antiSMASH versions prior to antiSMASH 5, and experimentally demonstrated that it directs the biosynthesis of two metabolites, one of which was identified as sphydrofuran. Synteruptor is also a valuable resource for the delineation of individual SMBGCs within antiSMASH regions that may encompass multiple clusters, and for refining the boundaries of these SMBGCs.
PubMed: 38915823
DOI: 10.1093/nargab/lqae069 -
The Journal of Antibiotics Jun 2024Two new aromatic tenvermectins (TVMs), 13-oleandrosyl-oleandrosyloxy ST906 (1) and aromatic TVM B (2), were isolated from the fermentation broth of Streptomyces...
Two new aromatic tenvermectins (TVMs), 13-oleandrosyl-oleandrosyloxy ST906 (1) and aromatic TVM B (2), were isolated from the fermentation broth of Streptomyces avermitilis HU02-06. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data. Bioassay test showed that these two new tenvermectins exhibited weak nematocidal activity against Bursaphelenchus xylophilus and moderate cytotoxic activity against tumor cell lines HepG2 and HCT116.
PubMed: 38914796
DOI: 10.1038/s41429-024-00754-y -
World Journal of Microbiology &... Jun 2024This study explores the biosynthesis of silver nanoparticles (AgNPs) using the Streptomyces tuirus S16 strain, presenting an eco-friendly alternative to mitigate the...
Enhanced biosynthesis of coated silver nanoparticles using isolated bacteria from heavy metal soils and their photothermal-based antibacterial activity: integrating Response Surface Methodology (RSM) Hybrid Artificial Neural Network (ANN)-Genetic Algorithm (GA) strategies.
This study explores the biosynthesis of silver nanoparticles (AgNPs) using the Streptomyces tuirus S16 strain, presenting an eco-friendly alternative to mitigate the environmental and health risks of chemical synthesis methods. It focuses on optimizing medium culture conditions, understanding their physicochemical properties, and investigating their potential photothermal-based antibacterial application. The S16 strain was selected from soils contaminated with heavy metals to exploit its ability to produce diverse bioactive compounds. By employing the combination of Response Surface Methodology (RSM) and Artificial Neural Network (ANN)-Genetic Algorithm (GA) strategies, we optimized AgNPs synthesis, achieving an improvement of nearly 2.45 times the initial yield under specific conditions (Bennet's medium supplemented with glycerol [5 g/L] and casamino-acid [3 g/L] at 30 °C for 72 h). A detailed physicochemical characterization was conducted. Notably, the AgNPs were well dispersed, and a carbonaceous coating layer on their surface was confirmed using energy-dispersive X-ray spectroscopy. Furthermore, functional groups were identified using Fourier-transform infrared spectroscopy, which helped enhance the AgNPs' stability and biocompatibility. AgNPs also demonstrated efficient photothermal conversion under light irradiation (0.2 W/cm), with temperatures increasing to 41.7 °C, after 30 min. In addition, treatment with light irradiation of E. coli K-12 model effectively reduced the concentration of AgNPs from 105 to 52.5 µg/mL, thereby enhancing the efficacy of silver nanoparticles in contact with the E. coli K-12.
Topics: Silver; Metal Nanoparticles; Anti-Bacterial Agents; Neural Networks, Computer; Soil Microbiology; Metals, Heavy; Algorithms; Streptomyces; Microbial Sensitivity Tests; Soil Pollutants; Escherichia coli; Spectroscopy, Fourier Transform Infrared
PubMed: 38913279
DOI: 10.1007/s11274-024-04048-1 -
AMB Express Jun 2024
PubMed: 38913277
DOI: 10.1186/s13568-024-01724-1 -
ACS Chemical Biology Jun 2024tRNA modifications help maintain tRNA structure and facilitate translation and stress response. Found in all three kingdoms of life, mA tRNA modification occurs in the T...
tRNA modifications help maintain tRNA structure and facilitate translation and stress response. Found in all three kingdoms of life, mA tRNA modification occurs in the T loop of many tRNAs, stabilizes tertiary tRNA structure, and impacts translation. MA in the T loop is reversible by three mammalian demethylase enzymes, which bypasses the need of turning over the tRNA molecule to adjust its mA levels in cells. However, no prokaryotic tRNA demethylase enzyme has been identified that acts on endogenous RNA modifications. Using as a model organism, we confirmed the presence and quantitative mA tRNA signatures using mass spectrometry and high-throughput tRNA sequencing. We identified two RNA demethylases that can remove mA in tRNA and validated the activity of a previously annotated tRNA mA writer. Using single-gene knockouts of these erasers and the mA writer, we found dynamic changes of mA levels in many tRNAs under stress conditions. Phenotypic characterization highlighted changes in their growth and altered antibiotic production. Our identification of the first prokaryotic tRNA demethylase enzyme paves the way for investigating new mechanisms of translational regulation in bacteria.
PubMed: 38912606
DOI: 10.1021/acschembio.4c00278 -
Journal of Hazardous Materials Jun 2024Phosphate-solubilizing bacteria (PSB) are important but often overlooked regulators of uranium (U) cycling in soil. However, the impact of PSB on uranate fixation...
Phosphate-solubilizing bacteria (PSB) are important but often overlooked regulators of uranium (U) cycling in soil. However, the impact of PSB on uranate fixation coupled with the decomposition of recalcitrant phosphorus (P) in mining land remains poorly understood. Here, we combined gene amplicon sequencing, metagenome and metatranscriptome sequencing analysis and strain isolation to explore the effects of PSB on the stabilization of uranate and P availability in U mining areas. We found that the content of available phosphorus (AP), carbonate-U and Fe-Mn-U oxides in tailings was significantly (P < 0.05) higher than their adjacent soils. Also, organic phosphate mineralizing (PhoD) bacteria (e.g., Streptomyces) and inorganic phosphate solubilizing (gcd) bacteria (e.g., Rhodococcus) were enriched in tailings and soils, but only organic phosphate mineralizing-bacteria substantially contributed to the AP. Notably, most genes involved in organophosphorus mineralization and uranate resistance were widely present in tailings rather than soil. Comparative genomics analyses supported that organophosphorus mineralizing-Streptomyces species could increase soil AP content and immobilize U(VI) through organophosphorus mineralization (e.g., PhoD, ugpBAEC) and U resistance related genes (e.g., petA). We further demonstrated that the isolated Streptomyces sp. PSBY1 could enhance the U(VI) immobilization mediated by the NADH-dependent ubiquinol-cytochrome c reductase (petA) through decomposing organophosphorous compounds. This study advances our understanding of the roles of PSB in regulating the fixation of uranate and P availability in U tailings.
PubMed: 38908177
DOI: 10.1016/j.jhazmat.2024.134975 -
Nucleic Acids Research Jun 2024Filamentous Actinobacteria, recently renamed Actinomycetia, are the most prolific source of microbial bioactive natural products. Studies on biosynthetic gene clusters...
Filamentous Actinobacteria, recently renamed Actinomycetia, are the most prolific source of microbial bioactive natural products. Studies on biosynthetic gene clusters benefit from or require chromosome-level assemblies. Here, we provide DNA sequences from >1000 isolates: 881 complete genomes and 153 near-complete genomes, representing 28 genera and 389 species, including 244 likely novel species. All genomes are from filamentous isolates of the class Actinomycetia from the NBC culture collection. The largest genus is Streptomyces with 886 genomes including 742 complete assemblies. We use this data to show that analysis of complete genomes can bring biological understanding not previously derived from more fragmented sequences or less systematic datasets. We document the central and structured location of core genes and distal location of specialized metabolite biosynthetic gene clusters and duplicate core genes on the linear Streptomyces chromosome, and analyze the content and length of the terminal inverted repeats which are characteristic for Streptomyces. We then analyze the diversity of trans-AT polyketide synthase biosynthetic gene clusters, which encodes the machinery of a biotechnologically highly interesting compound class. These insights have both ecological and biotechnological implications in understanding the importance of high quality genomic resources and the complex role synteny plays in Actinomycetia biology.
PubMed: 38908028
DOI: 10.1093/nar/gkae523 -
Biomolecular NMR Assignments Jun 2024Signalosomes are high-order protein machineries involved in complex mechanisms controlling regulated immune defense and cell death execution. The immune response is...
Signalosomes are high-order protein machineries involved in complex mechanisms controlling regulated immune defense and cell death execution. The immune response is initiated by the recognition of exogeneous or endogenous signals, triggering the signalosome assembly process. The final step of signalosome fate often involves membrane-targeting and activation of pore-forming execution domains, leading to membrane disruption and ultimately cell death. Such cell death-inducing domains have been thoroughly characterized in plants, mammals and fungi, notably for the fungal cell death execution protein domain HeLo. However, little is known on the mechanisms of signalosome-based immune response in bacteria, and the conformation of cell death executors in bacterial signalosomes is still poorly characterized. We recently uncovered the existence of NLR signalosomes in various multicellular bacteria and used genome mining approaches to identify putative cell death executors in Streptomyces olivochromogenes. These proteins contain a C-terminal amyloid domain involved in signal transmission and a N-terminal domain, termed BELL for Bacteria analogous to fungal HeLL (HeLo-like), presumably responsible for membrane-targeting, pore-forming and cell death execution. In the present study, we report the high yield expression of S. olivochromogenes BELL2 and its characterization by solution NMR spectroscopy. BELL is folded in solution and we report backbone and sidechain assignments. We identified five α-helical secondary structure elements and a folded core much smaller than its fungal homolog HeLo. This study constitutes the first step toward the NMR investigation of the full-length protein assembly and its membrane targeting.
PubMed: 38907837
DOI: 10.1007/s12104-024-10183-5