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MBio Aug 2023Polyphenols are abundant in nature, and their anaerobic biodegradation by gut and soil bacteria is a topic of great interest. The O requirement of phenol oxidases is...
Polyphenols are abundant in nature, and their anaerobic biodegradation by gut and soil bacteria is a topic of great interest. The O requirement of phenol oxidases is thought to explain the microbial inertness of phenolic compounds in anoxic environments, such as peatlands, termed the enzyme latch hypothesis. A caveat of this model is that certain phenols are known to be degraded by strict anaerobic bacteria, although the biochemical basis for this process is incompletely understood. Here, we report the discovery and characterization of a gene cluster in the environmental bacterium for the degradation phloroglucinol (1,3,5-trihydroxybenzene), a key intermediate in the anaerobic degradation of flavonoids and tannins, which constitute the most abundant polyphenols in nature. The gene cluster encodes the key C-C cleavage enzyme dihydrophloroglucinol cyclohydrolase, as well as ()-3-hydroxy-5-oxo-hexanoate dehydrogenase and triacetate acetoacetate-lyase, which enable phloroglucinol to be utilized as a carbon and energy source. Bioinformatics studies revealed the presence of this gene cluster in phylogenetically and metabolically diverse gut and environmental bacteria, with potential impacts on human health and carbon preservation in peat soils and other anaerobic environmental niches. IMPORTANCE This study provides novel insights into the microbiota's anaerobic metabolism of phloroglucinol, a critical intermediate in the degradation of polyphenols in plants. Elucidation of this anaerobic pathway reveals enzymatic mechanisms for the degradation of phloroglucinol into short-chain fatty acids and acetyl-CoA, which are used as a carbon and energy source for bacterium growth. Bioinformatics studies suggested the prevalence of this pathway in phylogenetically and metabolically diverse gut and environmental bacteria, with potential impacts on carbon preservation in peat soils and human gut health.
Topics: Humans; Phloroglucinol; Anaerobiosis; Bacteria; Bacteria, Anaerobic; Phenols; Polyphenols; Soil
PubMed: 37341492
DOI: 10.1128/mbio.01099-23 -
Characterisation of Fasting and Postprandial NMR Metabolites: Insights from the ZOE PREDICT 1 Study.Nutrients Jun 2023Postprandial metabolomic profiles and their inter-individual variability are not well characterised. Here, we describe postprandial metabolite changes, their...
BACKGROUND
Postprandial metabolomic profiles and their inter-individual variability are not well characterised. Here, we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability, following a standardised meal in the ZOE PREDICT 1 cohort.
METHODS
In the ZOE PREDICT 1 study ( = 1002 (NCT03479866)), 250 metabolites, mainly lipids, were measured by a Nightingale NMR panel in fasting and postprandial (4 and 6 h after a 3.7 MJ mixed nutrient meal, with a second 2.2 MJ mixed nutrient meal at 4 h) serum samples. For each metabolite, inter- and intra-individual variability over time was evaluated using linear mixed modelling and intraclass correlation coefficients (ICC) were calculated.
RESULTS
Postprandially, 85% (of 250 metabolites) significantly changed from fasting at 6 h (47% increased, 53% decreased; Kruskal-Wallis), with 37 measures increasing by >25% and 14 increasing by >50%. The largest changes were observed in very large lipoprotein particles and ketone bodies. Seventy-one percent of circulating metabolites were strongly correlated (Spearman's rho >0.80) between fasting and postprandial timepoints, and 5% were weakly correlated (rho <0.50). The median ICC of the 250 metabolites was 0.91 (range 0.08-0.99). The lowest ICCs (ICC <0.40, 4% of measures) were found for glucose, pyruvate, ketone bodies (β-hydroxybutyrate, acetoacetate, acetate) and lactate.
CONCLUSIONS
In this large-scale postprandial metabolomic study, circulating metabolites were highly variable between individuals following sequential mixed meals. Findings suggest that a meal challenge may yield postprandial responses divergent from fasting measures, specifically for glycolysis, essential amino acid, ketone body and lipoprotein size metabolites.
Topics: Humans; Blood Glucose; Fasting; Ketone Bodies; Lipoproteins; Magnetic Resonance Spectroscopy; Metabolomics; Postprandial Period; Triglycerides; Clinical Studies as Topic
PubMed: 37299601
DOI: 10.3390/nu15112638 -
Frontiers in Physiology 2023
PubMed: 37260594
DOI: 10.3389/fphys.2023.1197768 -
Journal of Advanced Pharmaceutical... 2023Quinoline and its derivatives are known to have various biological activities such as antibacterial and antioxidant. Therefore, this study aims to synthesize quinoline...
Quinoline and its derivatives are known to have various biological activities such as antibacterial and antioxidant. Therefore, this study aims to synthesize quinoline moiety from isatin and ethyl acetoacetate by Pfitzinger reaction under acidic conditions. The benzimidazole derivative was synthesized from quinoline and o-phenylenediamine by a solvent-less reaction, while the hydrazone derivative was formed by the reaction with hydrazine hydrate and aromatic aldehyde. In addition, 4-hydroxybenzaldehyde was used as an aromatic aldehyde. The four compounds formed were characterized by thin-layer chromatography (TLC), melting point measurement, Fourier-transform infrared, liquid chromatography-mass spectrometry, and ultraviolet-visible spectrophotometry. They were also evaluated for their antioxidant and antimicrobial activities using the 2,2-diphenyl-1-picrylhydrazyl assay and the disc diffusion method, respectively. All compounds showed weak antioxidant activity compared to ascorbic acid; the quinoline-hydrazone derivative showed the best antioxidant activity with IC = 843.52 ppm, while the IC value for quinoline-benzimidazole was 4784.66 ppm. All synthesized compounds have not been confirmed to be effective against and bacteria in a concentration range of 75-1000 ppm. The bioactive compounds based on the quinoline-hydrazone and benzimidazole structures have been successfully synthesized and tested for their activity as antioxidant and antimicrobial agents.
PubMed: 37255873
DOI: 10.4103/japtr.japtr_599_22 -
Applied and Environmental Microbiology Jun 2023Ketone bodies, including acetoacetate, 3-hydroxybutyrate, and acetone, are produced in the liver of animals during glucose starvation. Enzymes for the metabolism of...
Ketone bodies, including acetoacetate, 3-hydroxybutyrate, and acetone, are produced in the liver of animals during glucose starvation. Enzymes for the metabolism of ()-3-hydroxybutyrate have been extensively studied, but little is known about the metabolism of its enantiomer ()-3-hydroxybutyrate. Here, we report the characterization of a novel pathway for the degradation of ()-3-hydroxybutyrate in anaerobic bacteria. We identify and characterize a stereospecific ()-3-hydroxylbutyrate dehydrogenase (3SHBDH) from Desulfotomaculum ruminis, which catalyzes the reversible NAD(P)H-dependent reduction of acetoacetate to form ()-3-hydroxybutyrate. 3SHBDH also catalyzes oxidation of d-threonine (2, 3) and l-allo-threonine (2, 3), consistent with its specificity for β-(3)-hydroxy acids. Isothermal calorimetry experiments support a sequential mechanism involving binding of NADH prior to ()-3-hydroxybutyrate. Homologs of 3SHBDH are present in anaerobic fermenting and sulfite-reducing bacteria, and experiments with Clostridium pasteurianum showed that 3SHBDH, acetate CoA-transferase (YdiF), and ()-3-hydroxybutyryl-CoA dehydrogenase (Hbd) are involved together in the degradation of ()-3-hydroxybutyrate as a carbon and energy source for growth. ()-3-hydroxybutyrate is a human metabolic marker and a chiral precursor for chemical synthesis, suggesting potential applications of 3SHBDH in diagnostics or the chemicals industry. ()-3-hydroxybutyrate is well studied as a component of ketone bodies produced by the liver and of bacterial polyesters. However, the biochemistry of its enantiomer ()-3-hydroxybutyrate is poorly understood. This study describes the identification and characterization of a stereospecific ()-3-hydroxylbutyrate dehydrogenase and its function in a metabolic pathway for the degradation of ()-3-hydroxybutyrate as a carbon and energy source in anaerobic bacteria. ()-3-hydroxybutyrate is a mammalian metabolic marker and a precursor for chemical synthesis and bioplastics, suggesting potential applications of these enzymes in diagnostics and biotechnology.
Topics: Animals; Humans; 3-Hydroxybutyric Acid; Bacteria, Anaerobic; Acetoacetates; Hydroxybutyrate Dehydrogenase; Hydroxybutyrates; Ketone Bodies; 3-Hydroxyacyl-CoA Dehydrogenase; Bacteria; Carbon; Threonine; Mammals
PubMed: 37255440
DOI: 10.1128/aem.00366-23 -
Journal of Neuroimmunology Jun 2023To prioritize circulating metabolites that likely play causal roles in the pathogenesis of multiple sclerosis (MS). Two-sample Mendelian randomization analysis was...
To prioritize circulating metabolites that likely play causal roles in the pathogenesis of multiple sclerosis (MS). Two-sample Mendelian randomization analysis was performed to estimate the causal effects of 571 circulating metabolites on the risk of MS. Genetic instruments for circulating metabolites were obtained from three previous genome-wide association studies (GWAS) of the blood metabolome (N = 7824; 24,925; and 115,078; respectively), while genetic associations with MS were from a large GWAS by the International Multiple Sclerosis Genetics Consortium (14,802 cases and 26,703 control). The primary analysis was performed with the multiplicative random-effect inverse variance-weighted method, while multiple sensitivity analyses were conducted with the weighted median, weighted mode, MR-Egger, and MR-PRESSO. A total of 29 metabolites had suggestive evidence of causal associations with MS. Genetically instrumented levels of serine (OR = 1.56, 95% CI = 1.25-1.95), lysine (OR = 1.18, 95% CI = 1.01-1.38), acetone (OR = 2.45, 95% CI = 1.02-5.90), and acetoacetate (OR = 2.47, 95% CI = 1.14-5.34) were associated with a higher MS risk. Total cholesterol and phospholipids in large very-low-density lipoprotein were associated with a lower MS risk (OR = 0.83, 95% CI = 0.69-1.00; OR = 0.80, 95% CI = 0.68-0.95), but risk-increasing associations (OR = 1.20, 95% CI = 1.04-1.40; OR = 1.13, 95% CI = 1.00-1.28) were observed for the same two lipids in very large high-density lipoprotein. Our metabolome-wide Mendelian randomization study prioritized a list of circulating metabolites, such as serine, lysine, acetone, acetoacetate, and lipids, that likely have causal associations with MS.
Topics: Humans; Acetoacetates; Acetone; Genome-Wide Association Study; Lysine; Mendelian Randomization Analysis; Multiple Sclerosis; Metabolome; Serine; Polymorphism, Single Nucleotide
PubMed: 37207441
DOI: 10.1016/j.jneuroim.2023.578105 -
Analytical and Bioanalytical Chemistry Jul 2023Early, express, and reliable detection of cancer can provide a favorable prognosis and decrease mortality. Tumor biomarkers have been proven to be closely related to...
Early, express, and reliable detection of cancer can provide a favorable prognosis and decrease mortality. Tumor biomarkers have been proven to be closely related to tumor occurrence and development. Conventional tumor biomarker detection based on genomic, proteomic, and metabolomic methods is time and equipment-consuming and always needs a specific target marker. Surface-enhanced Raman scattering (SERS), as a non-invasive ultrasensitive and label-free vibrational spectroscopy technique, can detect cancer-related biomedical changes in biofluids. In this paper, 110 serum samples were collected from 30 healthy controls and 80 cancer patients (including 30 bladder cancer (BC), 30 adrenal cancer (AC), and 20 acute myeloid leukemia (AML)). One microliter of blood serum was mixed with 1 μl silver colloid and then was air-dried for SERS measurements. After spectral data augmentation, one-dimensional convolutional neural network (1D-CNN) was proposed for precise and rapid identification of healthy and three different cancers with high accuracy of 98.27%. After gradient-weighted class activation mapping (Grad-CAM) based spectral interpretation, the contributions of SERS peaks corresponding to biochemical substances indicated the most potential biomarkers, i.e., L-tyrosine in bladder cancer; acetoacetate and riboflavin in adrenal cancer and phospholipids, amide-I, and α-Helix in acute myeloid leukemia, which might provide an insight into the mechanism of intelligent diagnosis of different cancers based on label-free serum SERS. The integration of label-free SERS and deep learning has great potential for the rapid, reliable, and non-invasive detection of cancers, which may significantly improve the precise diagnosis in clinical practice.
Topics: Humans; Deep Learning; Proteomics; Adrenal Gland Neoplasms; Urinary Bladder Neoplasms; Biomarkers, Tumor; Spectrum Analysis, Raman
PubMed: 37195443
DOI: 10.1007/s00216-023-04730-7 -
Molecules (Basel, Switzerland) May 2023A series of new [1,2,4]triazolo[4,3-a]pyrimidine derivatives was prepared using a one-pot three-component synthesis from 5-amino-1-phenyl-1-1,2,4-triazoles, aromatic...
A series of new [1,2,4]triazolo[4,3-a]pyrimidine derivatives was prepared using a one-pot three-component synthesis from 5-amino-1-phenyl-1-1,2,4-triazoles, aromatic aldehydes and ethyl acetoacetate. The compound structures were confirmed by IR, H-NMR, C-NMR, HRMS and X-ray analyses. The biological activity of these compounds as antitumor agents was evaluated. Their antitumor activities against cancer cell lines (MDA-MB-231 and MCF-7) were tested by the MTT in vitro method. Among them, compounds and displayed the best antitumor activity with IC values of 17.83 μM and 19.73 μM against MDA-MB-231 and MCF-7 cell lines, respectively, compared to the Cisplatin reference.
Topics: Humans; Pyrimidines; Antineoplastic Agents; Cisplatin; MCF-7 Cells; Magnetic Resonance Spectroscopy; Drug Screening Assays, Antitumor; Structure-Activity Relationship; Cell Proliferation; Cell Line, Tumor; Molecular Structure
PubMed: 37175327
DOI: 10.3390/molecules28093917 -
Frontiers in Neuroscience 2023Studies have shown an association between depression and circulating metabolites, but the causal relationship between them has not been elucidated. The purpose of this...
BACKGROUND
Studies have shown an association between depression and circulating metabolites, but the causal relationship between them has not been elucidated. The purpose of this study was to elucidate the causal relationship between circulating metabolites and depression and to explore the role of circulating metabolites in depression.
METHODS
In this study, the top single-nucleotide polymorphisms (SNPs) associated with circulating metabolites ( = 24,925) and depression ( = 322,580) were obtained based on the publicly available genome-wide association study using two-sample Mendelian randomization (MR). SNP estimates were summarized through inverse variance weighted, MR Egger, weighted median, MR pleiotropy residual sum and outlier, and "leave-one-out" methods.
RESULTS
Apolipoprotein A-I (OR 0.990, 95% CI 981-0.999) and glutamine (OR 0.985, 95% CI 0.972-0.997) had protective causal effects on depression, whereas acetoacetate (OR 1.021, 95% CI 1.009-1.034), glycoproteins (OR 1.005, 95% CI 1.000-1.009), isoleucine (OR 1.013, 95% CI 1.002-1.024), and urea (OR 1.020, 95% CI 1.000-1.039) had an anti-protective effect on depression. Reversed MR showed no effect of depression on the seven circulating metabolites.
CONCLUSION
In this study, MR analysis showed that apolipoprotein A-I and glutamine had a protective effect on depression, and acetoacetate, glycoprotein, isoleucine, glucose, and urea may be risk factors for depression. Therefore, further research must be conducted to translate the findings into practice.
PubMed: 37152596
DOI: 10.3389/fnins.2023.1146613 -
Acta Crystallographica. Section E,... Apr 2023The mol-ecular and crystal structure of the title binuclear Zn complex, [Zn(CHO)(CHOH)], with enolated anionic -butyl-aceto-acetate and ethanol was analysed. The...
The mol-ecular and crystal structure of the title binuclear Zn complex, [Zn(CHO)(CHOH)], with enolated anionic -butyl-aceto-acetate and ethanol was analysed. The coordination polyhedra of the Zn atoms are distorted octa-hedra formed by six oxygen atoms that belong to three ligand mol-ecules and a coordinated ethanol mol-ecule. In the crystal phase, alternating layers can be distinguished parallel to the plane. A Hirshfeld surface analysis showed that there are no strong inter-molecular inter-actions in the structure. The most significant contributions to the overall crystal packing are from H⋯H inter-molecular contacts.
PubMed: 37151829
DOI: 10.1107/S2056989023003377