Search Results (122)

Tryptophan is synthesized in microorganisms via a five-step enzymatic pathway originating from chorismate, which is a product of the shikimate pathway. As a biosynthetic precursor to a wide range of high-value compounds such as indole-3-acetic acid, indigo, indirubin, and violacein, this pathway has been a central target for metabolic engineering to enhance microbial production. Anthranilate phosphoribosyltransferase (AnPRT) catalyzes the second step of the pathway by transferring a phosphoribosyl group from PRPP to anthranilate, forming phosphoribosyl anthranilate (PRA). AnPRT, the sole member of class IV phosphoribosyltransferases, adopts a unique fold and functions as a homodimer. While the structural basis of AnPRT activity has been elucidated in several organisms, thermostable variants remain underexplored despite their relevance for high-temperature bioprocessing. In this study, the crystal structure of AnPRT from the thermophilic archaeon Methanocaldococcus jannaschii (MjAnPRT) was determined at a 2.16 Å resolution. The enzyme exhibits a conserved dimeric architecture and key catalytic motifs. Comparative structural analysis with mesophilic and hyper thermophilic homologs revealed that MjAnPRT possesses enhanced local stability in catalytically important regions and strengthened inter-subunit interactions. These features likely contribute to its thermostability and provide a valuable framework for the rational design of robust AnPRTs for industrial and synthetic biology applications. Full article

Serotoninomics is an expanding field that focuses on the comprehensive study of the serotoninergic system, including serotonin’s biosynthesis, metabolism, and regulation, as well as related scientific methodologies 5-hydroxytryptamine (5-HT). This field explores serotonin’s complex roles in various physiological and pathological contexts. The essential amino acid tryptophan (Trp) is a precursor for several metabolic and catabolic pathways, with the kynurenine (KYN) pathway being particularly significant, representing about 95% of Trp metabolism. In contrast, only a small portion (1–2%) of dietary Trp enters the serotonin pathway. Anthranilic acid (AA), a metabolite in the KYN pathway, has emerged as a potential biomarker and therapeutic target for schizophrenia. Elevated serum AA levels in patients with schizophrenia have been associated with neurotoxic effects and disruptions in neurotransmission, suggesting AA’s critical role in the disorder’s pathophysiology. Furthermore, the 5-HT_2A receptor’s involvement is particularly noteworthy, especially in relation to schizophrenia’s positive symptoms. Recent findings indicate that 5-HT_2A receptor hyperactivity is linked to positive symptoms of schizophrenia, such as hallucinations and delusions. This study investigates serotoninomics’ implications for neuropsychiatric disorders, focusing on AA in schizophrenia and analysing recent research on serotonin signalling pathways and AA’s neurochemical effects. Understanding the roles of the 5-HT_2A receptor and AA in neuropsychiatric disorders could lead to the development of more precise and less invasive diagnostic tools, specific therapeutic strategies, and improved clinical outcomes. Ongoing research is essential to uncover these pathways’ exact mechanisms and therapeutic potential, thereby advancing personalised medicine and innovative treatments in neuropsychiatry. Full article

Background/Objectives: Understanding metabolome adjustment under saline–alkaline conditions is crucial for enhancing crop tolerance capacity and ensuring food security. Although soil salinization impairs wheat seedlings’ growth, metabolome plasticity under saline–alkaline stress remains poorly understood. Here, we delved into dynamic physiological and metabolome shifts in wheat seedlings grown on SAS (saline–alkaline soil) on the 7th and 15th days post-germination (DPG). Methods: A self-developed and cultivated high-generation salt–alkali wheat variety (011) was grown on SAS and control soil, followed by comparative physiological, biochemical, and metabolomics analyses of seedlings. Results: The seedlings’ saline–alkaline stress responses were developmentally regulated with reduced growth, increasing accumulation of proline and soluble sugars, and differential antioxidant response. LC-MS-based global metabolomics analysis revealed significant metabolite profile differences, with 367 and 485 differential metabolites identified on the 7th and 15th DPG, respectively, between control and treatment. Upregulation of saccharides, flavonoids, organic acids (citrate cycle-related), phenolic acids, amino acids and derivatives, phytohormones, and sphingolipid metabolism was essential for seedlings’ growth on SAS. The key induced metabolites in seedlings grown on SAS include saccharic acid, trehalose, sucrose, glucose, L-citramalic acid, phellodendroside, scutellarin, anthranilate-1-O-sophoroside, lavandulifolioside, N-methyl-L-glutamate, etc. Up-regulated phytohormones include abscisic acid (3.8-fold, 7th DPG and 3.18-fold, 15th DPG), jasmonic acid (1.93-fold, 15th DPG), and jasmonoyl isoleucine (2.03-fold, 15th DPG). Conclusions: Our findings highlight the importance of ABA and jasmonic acid in regulating salt–alkali tolerance in wheat seedlings. Moreover, this study depicts key pathways involved in salt–alkali tolerance in wheat seedlings and unveils key DMs, offering resources for boosting wheat production on SAS. Full article

Schistosomes are intravascular parasitic worms that cause the debilitating tropical disease schistosomiasis, affecting >200 million people worldwide. How the worms survive within the body of immunocompetent hosts for many years is unclear. Here, using chromatography and mass spectrometry, we report on the ex vivo ability of adult Schistosoma mansoni worms to modulate the levels of 27 small molecule (often immunomodulatory) metabokines in murine plasma. Schistosomes significantly alter the relative amounts of most (16) of these molecules. Three (inosine, genistein, and glucose) are significantly decreased in the presence of the parasites. While levels of several immunomodulatory metabolites from the kynurenine pathway (kynurenine, kynurenic acid, and xanthurenic acid) remain unchanged, levels of anthranilate (an endogenous regulator of innate immunity) are significantly increased. Of particular interest are increases in levels of metabolites that are known to skew immune responses in a manner that is seen following natural schistosome infection, such as by promoting Th2 immunity (succinate), Treg generation (lactate) and M2 macrophage polarization (lactate and succinate). In addition, significant increases are also observed for 2-hydroxyglutarate, adenine, hypoxanthine, xanthine, myoinositol, betaine and N-acetylglucosamine. Each of these compounds can have immunosuppressive effects that could impact host immunological status and contribute to schistosome survival. Full article

Objective: The aim of this work is to investigate the impact of exercise on gut microbiome composition, serum metabolites, and their correlation with osteoarthritis (OA) severity. Methods: Thirty-six Sprague-Dawley (SD) rats were randomly divided into four groups: Sham rats without treadmill walking (Sham/Sed group, n = 9), Sham rats with treadmill walking 2 months (Sham/TW2M group, n = 9), PTOA rats without treadmill walking (PTOA/Sed group, n = 9), and PTOA rats with treadmill walking 2 months (PTOA/TW2M group, n = 9). The PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and destabilization of the medial meniscus (DMM). Histological evaluation and micro-CT analysis were performed to observe the pathological changes in cartilage and subchondral bone, respectively. Additionally, we conducted 16S rDNA sequencing of fecal samples and untargeted metabolomic analysis using liquid chromatography–mass spectrometry (LC–MS) of serum samples to detect the alteration of gut microbiota composition and metabolites. Results: Exercise effectively mitigated OA-related pathological changes, including articular cartilage degeneration and subchondral bone loss. Moreover, 16S rDNA sequencing analysis of gut microbiome revealed a decreased abundance of Bacteroidetes (p < 0.01), Bacteroidia (p < 0.01), Rikenellaceae (p < 0.01), [Paraprevotellaceae] (p < 0.01), and Paraprevotella (p < 0.01) but an increase in Firmicutes (p < 0.01) in PTOA/TW2M group rats compared with PTOA/Sed group as a response to exercise. In addition, the results of metabolomics analysis showed that exercise treatment contributed to the upregulation of Daidzein and Anthranilic acid and downregulation of 1-Palmitoyllysophosphatidylcholine. Moreover, the correlation analysis showed that Rikenellaceae significantly positively correlated with both OARSI (r = 0.81, p < 0.01) and Mankin score (r = 0.83, p < 0.01) and negatively correlated with the serum level of Anthranilic acid (r = −0.56, p < 0.01) and Daidzein (r = −0.46, p < 0.01). Conclusions: Exercise can effectively mitigate OA through slowing down articular cartilage degeneration and subchondral bone loss, modulating gut microbiota composition, and increasing beneficial metabolites. Full article

Background/Objectives: We aimed to discover genes with bimodal expression linked to patient outcomes, to reveal underlying oncogenotypes and identify new therapeutic insights in lung adenocarcinoma (LUAD). Methods: We performed meta-analysis to screen LUAD datasets for prognostic genes with bimodal expression patterns. Kynureninase (KYNU), a key enzyme in tryptophan catabolism, emerged as a top candidate. We then examined its relationship with LUAD mutations, metabolic alterations, immune microenvironment states, and expression patterns in human and mouse models using bulk and single-cell transcriptomics, metabolomics, and preclinical model datasets. Pan-cancer prognostic associations were also assessed. Results: Model-based clustering of KYNU expression outperformed median-based dichotomization in prognostic accuracy. KYNU was elevated in tumors with KEAP1 and STK11 co-mutations but remained a strong independent prognostic marker. Metabolomic analysis showed that KYNU-high tumors had increased anthranilic acid, a catalytic product, while maintaining stable kynurenine levels, suggesting a compensatory mechanism sustaining immunosuppressive signaling. Single-cell and bulk data showed KYNU expression was cancer cell-intrinsic in immune-cold tumors and myeloid-derived in immune-infiltrated tumors. In murine LUAD models, Kynu expression was predominantly immune-derived and uncoupled from Nrf2/Lkb1 signaling, indicating poor model fidelity. KYNU’s prognostic associations extended across cancer types, with poor outcomes in pancreatic and kidney cancers but favorable outcomes in melanoma, underscoring the need for lineage-specific considerations in therapy development. Conclusions:KYNU is a robust prognostic biomarker and potential immunometabolic target in LUAD, especially in STK11 and KEAP1 co-mutated tumors. Its cancer cell-intrinsic expression and immunosuppressive metabolic phenotype offer translational potential, though species-specific expression patterns pose challenges for preclinical modeling. Full article

Background: Intestinal ischemia reperfusion injury (IRI) is a harmful process that occurs during intestinal infarction and intestinal transplantation (ITx). It is characterized by severe inflammation which disrupts the mucosal barrier, causing bacterial translocation and sepsis. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) (TL) is a synthetic compound with powerful anti-inflammatory properties. Objective: To investigate the effect of pretreatment with TL in a validated rat model of intestinal IRI (60 min of ischemia). Methods: TL (650 mg/kg) was administered by oral gavage 24 and 2 h before the onset of ischemia. Experiment 1 examined 7-day survival in 3 study groups (sham, vehicle+IRI and TL+IRI, n = 10/group). In Experiment 2, the effects on the intestinal wall integrity and inflammation were studied after 60 min of reperfusion using 3 groups (sham, IRI and TL+IRI, n = 6/group). The following end-points were studied: L-lactate, intestinal fatty acid-binding protein (I-FABP), histology, intestinal permeability, endotoxin translocation, pro- and anti-inflammatory cytokines and heme oxygenase-1 (HO-1) levels. Experiment 3 examined the role of HO-1 upregulation in TL pretreatment, by blocking its expression using Zinc protoporphyrin (ZnPP) at 20 mg/kg vs. placebo (n = 6/group). Results: Intestinal IRI resulted in severe damage of the intestinal wall and a 10% 7-day survival. These alterations led to endotoxin translocation and upregulation of pro-inflammatory cytokines. TL pretreatment improved survival up to 50%, significantly reduced inflammation and protected the intestinal barrier. The HO-1 inhibitor ZnPP, abolished the protective effect of TL. Conclusions: TL pretreatment improves survival by protecting the intestinal barrier function, decreasing inflammation and endotoxin translocation, through upregulation of HO-1.This rat study of severe intestinal ischemia reperfusion injury demonstrates a novel role for Tranilast as a potential therapy. Administration of Tranilast led to a marked reduction in mortality, inflammation and intestinal permeability and damage. The study proved that Tranilast functions through upregulation of heme oxygenase-1. Full article

Strawberry fruits accumulate nutritionally critical anthocyanins and phytochemicals through light=quality-dependent metabolic regulation. This review systematically examines spectral modulation strategies for enhancing anthocyanin biosynthesis and fruit quality parameters. We demonstrate that dual red (660 nm) and blue (450 nm) irradiation optimally activates the flavonoid pathway, co-upregulating structural genes (CHS, F3H, DFR, ANS) and regulatory factors (FaMYB10, FaHY5). Mechanistic analyses reveal that blue light preferentially induces upstream phenylpropanoid enzymes (PAL, C4H, CHI), while red light enhances proanthocyanidin production through differential induction of LAR and ANR. Strategic supplementation with UV-C (254 nm, 1–2 kJ/m²/d) and far-red (730 nm, 15 μmol·m⁻²·s⁻¹) improves anthocyanin spatial distribution via stress-mediated epidermal accumulation. Spectral optimization further coordinates flavor development by (1) balancing sucrose–hexose ratios through FaSPS1 modulation, (2) reducing organic acid content via FaMYB44.2 suppression, and (3) amplifying volatile esters (e.g., methyl anthranilate) through SAAT induction. Postharvest UV-C treatment (4 kJ/m²) extends shelf life by 30–35% through microbial inhibition and antioxidant system activation. Practical implementation frameworks propose phase-specific LED protocols related to vegetative growth (R:B = 3:1), flowering (R:B = 1:1), and maturation (R:B = 4:1) stages integrated with environmental sensors in controlled agriculture systems. These findings establish an actionable paradigm for photonic crop management, synergizing molecular precision with commercial horticultural operations to achieve sustainable yield enhancement (projected 22–28% increase) and nutraceutical enrichment. Full article

This study explores the potential anti-H1N1 Influenza A activity of bioactive compounds extracted from Streptomyces ardesiacus, a marine-derived microorganism known for producing diverse secondary metabolites. Four major compounds—1-acetyl-β-carboline, 1H-indole-3-carbaldehyde, anthranilic acid, and indole-3-carboxylic acid—were isolated and characterized through NMR. Among these, the identified structure of 1-acetyl-β-carboline showed the highest IC₅₀ effect, with a dose of 9.71 μg/mL in anti-influenza assays. Using network pharmacology and molecular docking analyses, the interactions of these compounds with key proteins involved in H1N1 pathogenesis were examined. Protein–protein interaction (PPI) networks and Gene Ontology enrichment analysis revealed CDC25B, PARP1, and PTGS2 as key targets, associating these compounds with pathways related to catalytic activity, inflammation, and cell cycle regulation. The molecular docking results demonstrated that 1-acetyl-β-carboline exhibited binding affinities comparable to Tamiflu, the positive control drug, with LibDock scores of 81.89, 77.49, and 89.21 for CDC25B, PARP1, and PTGS2, respectively, compared to Tamiflu’s scores of 84.34, 86.13, and 91.29. These findings highlight the potential of the active compound 1-acetyl-β-carboline from S. ardesiacus as a novel anti-influenza agent, offering insights into their molecular mechanisms of action. The results support further in vitro and in vivo studies to validate the observed inhibitory mechanisms and therapeutic applications against H1N1 Influenza A. Full article

The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. The use of metabolomics approaches seems promising in speeding up and simplifying the diagnostic process in HFpEF patients, which can lead to earlier treatment initiation and better improvement of patient condition. The aim of this study was to develop a diagnostic panel of metabolites (metabolomic biomarkers) for the detection and diagnosis of HF with preserved ejection fraction. The study included 76 participants with hypertension, 36 of whom were diagnosed with HFpEF. The blood plasma metabolomic profile, including 72 metabolites, was detected using high-performance liquid chromatography combined with mass spectrometry. There were 18 statistically significant differences in concentrations of metabolites and 3 differences in their ratios between HFpEF and hypertension groups. The prognostic model for detecting the possibility of HFpEF included seven metabolites and two ratios: hexadecenoylcarnitine, arginine, trimethylamine-N-oxide, asymmetric dimethylarginine (ADMA), arginine/ADMA ratio, kynurenine, kynurenine/tryptophan, neopterin, and anthranilic acid. The area under the ROC curve was 0.981 ± 0.017. The resulting model was statistically significant (p < 0.001). The metabolomic panel could be considered as an addition to the present HFpEF laboratory diagnostic criteria for blood plasma analysis in clinical practice. Full article

Coffee cherry waste, a byproduct of coffee production, presents significant environmental challenges due to its large volume—approximately 20 million tons annually. The disposal of this waste, which includes pulp and mucilage, often leads to pollution of land and water systems, contributing to environmental degradation. Additionally, the high acidity and organic content of coffee cherry waste complicate its management, making it crucial to find sustainable solutions for its valorization and reuse in order to mitigate these ecological impacts. The purpose of this study is to investigate the efficiency and selectivity of various organic acid catalysts in the hydrothermal valorization of coffee cherry waste. The procedures were conducted using the liquid hot water (LHW) treatment for one hour with a 1:20 biomass/catalyst ratio and a 1 mm biomass particle size at 180 °C in 500 mL batch reactors modifying 10 different organic acids at 0.02 M. Concentrations of the valorized products (HMF, furfural, levulinic acid, formic acid, and sugars) were measured using HPLC-IR. Among the catalysts tested, adipic acid demonstrated the highest efficiency, with a total yield of 53.667%, showing significant selectivity towards formic acid (19.663%) and levulinic acid (11.291%). In contrast, butyric acid was the least efficient catalyst, yielding a total of 17.395% and showing minimal selectivity towards other compounds. Chloroacetic acid and benzoic acid were notable for their high selectivity towards sugars. Other catalysts, such as anthranilic acid, propanoic acid, and succinic acid, displayed moderate efficiency and selectivity, with balanced yields across various compounds. These findings highlight the importance of catalyst selection in optimizing the hydrothermal process for desired product outcomes. Full article

Advances in combinatorial synthesis and high-throughput screening methods have led to renewed interest in synthetic plant immunity activators as well as priming agents. 3,5-Dichloroanthranilic acid (3,5-DCAA) is a derivative of anthranilic acid that has shown potency in activating defence mechanisms in Arabidopsis and barley. Chemical biology, which is the interface of chemistry and biology, can make use of metabolomic approaches and tools to better understand molecular mechanisms operating in complex biological systems. Here we report on the untargeted metabolomic profiling of barley seedlings treated with 3,5-DCAA to gain deeper insights into the mechanism of action of this resistance inducer. Histochemical analysis revealed the production of reactive oxygen species in the leaves upon 3,5-DCAA infiltration. Subsequently, methanolic extracts from different time periods (12, 24, and 36 h post-treatment) were analysed by ultra-high-performance liquid chromatography hyphenated to a high-resolution mass spectrometer. Both unsupervised and supervised chemometric methods were used to reveal hidden patterns and highlight metabolite variables associated with the treatment. Based on the metabolites identified, both the phenylpropanoid and octadecanoid pathways appear to be main routes activated by 3,5-DCAA. Different classes of responsive metabolites were annotated with flavonoids, more specifically flavones, which were the most dominant. Given the limited understanding of this inducer, this study offers a metabolomic analysis of the response triggered by its foliar application in barley. This additional insight could help make informed decisions for the development of more effective strategies for crop protection and improvement, ultimately contributing to crop resilience and agricultural sustainability. Full article

Gracilaria fisheri (GF) is a red seaweed that is widely found in Southeast Asia and has gained attention for its potential bioactive compounds and versatile applications in food products. This study explored the potential of GF as a natural gelling agent in the development of sustainable strawberry-based drinking jelly. By utilizing GF at varying concentrations (0.2 (S1), 0.4 (S2), 0.6 (S3), 0.8 (S4), and 1.0% (S5)), the impact on the physicochemical, textural, phytochemical, and flavor profiles of the strawberry concentrate-based drinking jelly was examined. The results demonstrated that GF concentration significantly affected the color characteristics, structural development, and flavor profiles of the drinking jelly samples. Increasing GF levels progressively enhanced the lightness (L*) and redness (a*) values while reducing the yellowness (b*), with optimal visual appeal achieved in the S4 samples compared to others. Microscopical observations revealed that gel matrix development improved with GF concentrations up to 0.8% (S4), transitioning from a sparse, liquid-like structure at lower levels to a compact, over-gelated network at 1.0% (S5). Physicochemical parameters, including pH, total soluble solid (TSS), and TSS/titratable acidity (TA) ratios, increased with GF levels, contributing to a sweeter, less acidic product, while water activity (a_w) decreased, enhancing jelly stability. Viscosity and sulfate content increased significantly with GF concentration, indicating improved gel strength but reduced fluidity. Phytochemical analysis revealed that ascorbic acid (AsA) and total phenolic content (TPC) decreased progressively with higher GF levels, leading to a reduction in antioxidant activity (DPPH and ABTS). Volatile compound analysis identified alcohols, esters, and aldehydes as dominant contributors to the flavor profile. 1-Octanol (waxy, citrus-like) and methyl anthranilate (grape-like, sweet) increased substantially, while minor groups such as terpenoids and phenolic compounds contributed floral and woody notes. The findings suggest that S4 samples strike the optimal balance between texture, color, flavor, and antioxidant properties, achieving a cohesive, visually appealing, and flavorful drinking jelly suitable for commercial applications. Full article

Plant growth-promoting bacteria (PGPB) play a role in stimulating plant growth through mechanisms such as the synthesis of the phytohormone indole-3-acetic acid (IAA). The aims of this study were the characterization of IAA synthesis and degradation by the model aromatic-degrading bacterium Paraburkholderia xenovorans LB400, and its growth promotion of the Nicotiana tabacum plant. Strain LB400 was able to synthesize IAA (measured by HPLC) during growth in the presence of tryptophan and at least one additional carbon source; synthesis of anthranilic acid was also observed. RT-PCR analysis indicates that under these conditions, strain LB400 expressed the ipdC gene, which encodes indole-3-pyruvate decarboxylase, suggesting that IAA biosynthesis proceeds through the indole-3-pyruvate pathway. In addition, strain LB400 degraded IAA and grew on IAA as a sole carbon and energy source. Strain LB400 expressed the iacC and catA genes, which encode the α subunit of the aromatic-ring-hydroxylating dioxygenase in the IAA catabolic pathway and the catechol 1,2-dioxygenase, respectively, which may suggest a peripheral IAA pathway leading to the central catechol pathway. Notably, P. xenovorans LB400 promoted the growth of tobacco seedlings, increasing the number and the length of the roots. In conclusion, this study indicates that the versatile bacterium P. xenovorans LB400 is a PGPB. Full article

Cognitive impairment is a core feature of neurodevelopmental (schizophrenia) and aging-associated (mild cognitive impairment and Alzheimer’s dementia) neurodegenerative diseases. Limited efficacy of current pharmacological treatments warrants further search for new targets for nootropic interventions. The breakdown of myelin, a phospholipids axonal sheath that protects the conduction of nerve impulse between neurons, was proposed as a neuropathological abnormality that precedes and promotes the deposition of amyloid-β in neuritic plaques. The present review of the recent literature and our own pre- and clinical data suggest (for the first time) that the anthranilic acid (AA)-induced activation of microglial-expressed G-protein coupled receptor (GPR109A) inhibits cytosolic phospholipase A2 (cPLA2), an enzyme that triggers the degradation of myelin and consequently attenuates cognitive impairment. The present review suggests that the up-regulation of AA formation is a sex-specific compensatory (adaptive) reaction aimed to prevent/treat cognitive impairment. The AA–GPR109A–cPLA2–myelin–cognition cascade suggests new nootropic interventions, e.g., the administration of pegylated kynureninase, an enzyme that catalyzes AA formation from Kynurenine (Kyn), a tryptophane catabolite; pegylated interferon-alpha; central and peripheral Kyn aminotransferase inhibitors that increase availability of Kyn as a substrate for AA formation; and vagus nerve stimulation. The cascade predicts nootropic activity of exogenous GPR109A agonists that were designed and underwent clinical trials (unsuccessful) as anti-dyslipidemia agents. The proposed cascade might contribute to the pathogenesis of cognitive impairment. Data on AA in neurodegenerative disorders are scarce, and the proposed cascade needs further exploration in pre- and clinical studies Full article