Folitixorin Calcium

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces. This effort revealed principles governing functional crosstalk on a network level, divergent patterns of binding pocket conservation, and scaffolds for designing selective chemical probes. This structurally resolved ligand interactome mapping pipeline can be scaled to illuminate the native small-molecule networks of complete cells and potentially entire multi-cellular communities.

Edible bird's nest (EBN) is a functional food renowned for its numerous health benefits. While its nutritional and therapeutic value is well-documented, the metabolites contributing to the bioactivities of EBN remain poorly understood. This study aimed to identify the metabolites present in EBN subjected to different treatments, including double-boiled EBN (EBN_db), EBN hydrolysate (EBN_hydro), EBN fermented with Lactobacillus helveticus (EBN_LH), Latilactobacillus curvatus (EBN_LC), and Latilactobacillus sakei (EBN_LS) using liquid chromatography-mass spectrometry (LC-MS) and correlate the identified bioactive metabolites with the bioactivities of EBN. It was found that the fermented EBNs exhibited the highest number of metabolites, with 76 tentatively identified, followed by EBN_hydro (45) and EBN_db (37). Citric acid (1.97-4.48 g/kg) was present in all treated EBN samples, while L(+)-lactic acid (3.03-8.07 g/kg) and adipic acid (2.33-3.18 g/kg) were only found in fermented EBNs. Among the treated EBN samples, EBN_LC demonstrated the significantly highest (p ≤ 0.05) antioxidative (22.34 ± 0.41 % 1,1-diphenyl-2-picrylhydrazil radical scavenging activity), antihypertensive (5.46 ± 0.26 % angiotensin-converting enzyme inhibitory activity), and antihyperglycemic activities (6.48 ± 0.34 % α-amylase inhibitory activity). A total of 18 metabolites, including citric acid, 4-sphingenin, N-acetylcitrulline, 4-aminophenol, L(+)-lactic acid, 2-oxoadipate, sildenafil, formylglycinamidin-RP, 11β,17α,21-α-5β-pregnane-3,20-dione, 2-ketobutyric acid, homoserine, benzaldehyde, 1-pyrroline4-hydroxy-2-carboxylate, nortriptyline, 1-methylguanine, 3-hydroxy-trimethyllysine, 3-phenylpropionate, and reserphine were predicted as bioactive metabolites using the partial least squares discriminant analysis (PLS-DA). This study provides valuable insights into the metabolites present in EBN and serves as fundamental data for future investigations into the bioactive compounds responsible for its specific health benefits, potentially leading to the development of enhanced EBN-based functional foods.