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Chemistry (Weinheim An Der Bergstrasse,... Mar 2024Computational design advances enzyme evolution and their use in biocatalysis in a faster and more efficient manner. In this study, a synergistic approach integrating...
Computational design advances enzyme evolution and their use in biocatalysis in a faster and more efficient manner. In this study, a synergistic approach integrating tunnel engineering, evolutionary analysis, and force-field calculations has been employed to enhance the catalytic activity of D-lactonohydrolase (D-Lac), which is a pivotal enzyme involved in the resolution of racemic pantolactone during the production of vitamin B5. The best mutant, N96S/A271E/F274Y/F308G (M3), was obtained and its catalytic efficiency (k/K) was nearly 23-fold higher than that of the wild-type. The M3 whole-cell converted 20 % of DL-pantolactone into D-pantoic acid (D-PA, >99 % e.e.) with a conversion rate of 47 % and space-time yield of 107.1 g L h, demonstrating its great potential for industrial-scale D-pantothenic acid production. Molecular dynamics (MD) simulations revealed that the reduction in the steric hindrance within the substrate tunnel and conformational reconstruction of the distal loop resulted in a more favourable"catalytic" conformation, making it easier for the substrate and enzyme to enter their pre-reaction state. This study illustrates the potential of the distal residue on the pivotal loop at the entrance of the D-Lac substrate tunnel as a novel modification hotspot capable of reshaping energy patterns and consequently influencing the enzymatic activity.
Topics: Protein Engineering; Catalysis; Molecular Dynamics Simulation; 4-Butyrolactone
PubMed: 38217521
DOI: 10.1002/chem.202304164 -
International Journal of Molecular... Dec 2023Ochratoxin A (OTA) is one of the mycotoxins that poses a serious threat to human and animal health. Curcumin (CUR) is a major bioactive component of turmeric that...
Ochratoxin A (OTA) is one of the mycotoxins that poses a serious threat to human and animal health. Curcumin (CUR) is a major bioactive component of turmeric that provides multiple health benefits. CUR can reduce the toxicities induced by mycotoxins, but the underlying molecular mechanisms remain largely unknown. To explore the effects of CUR on OTA toxicity and identify the key regulators and metabolites involved in the biological processes, we performed metabolomic and transcriptomic analyses of livers from OTA-exposed mice. We found that CUR can alleviate the toxic effects of OTA on body growth and liver functions. In addition, CUR supplementation significantly affects the expressions of 1584 genes and 97 metabolites. Integrated analyses of transcriptomic and metabolomic data showed that the pathways including Arachidonic acid metabolism, Purine metabolism, and Cholesterol metabolism were significantly enriched. Pantothenic acid (PA) was identified as a key metabolite, the exogenous supplementation of which was observed to significantly alleviate the OTA-induced accumulation of reactive oxygen species and cell apoptosis. Further mechanistical analyses revealed that PA can downregulate the expression level of proapoptotic protein BAX, enhance the expression level of apoptosis inhibitory protein BCL2, and decrease the level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). This study demonstrated that CUR can alleviate the adverse effects of OTA by influencing the transcriptomic and metabolomic profiles of livers, which may contribute to the application of CUR in food and feed products for the prevention of OTA toxicity.
Topics: Humans; Animals; Mice; Curcumin; Drug-Related Side Effects and Adverse Reactions; Gene Expression Profiling; Mycotoxins; Chemical and Drug Induced Liver Injury; Ochratoxins
PubMed: 38203339
DOI: 10.3390/ijms25010168 -
Nutrients Dec 2023People with severe mental disorders often require special care. Other than institutionalized care, some organizations provide housing options and special care in the...
People with severe mental disorders often require special care. Other than institutionalized care, some organizations provide housing options and special care in the form of organized living. Few studies provide a detailed description of nutrient intake in this type of care. The aim of this prospective study was to assess nutritional status and adherence to dietary recommendations in both people with mental disorders (beneficiaries) and their caregivers. Across three levels of care, 46 beneficiaries and 19 caregivers participated in the study. The mean intakes of energy (kcal/day) and macro- and micronutrients (g/day) were estimated from a 3-day dietary record and compared with dietary reference values (DRVs) set by the European Food Safety Authority (EFSA). The majority of participants did not meet energy intake recommendations (kcal/day). The contribution of total fat to energy intake (% E) was higher than recommended in both beneficiaries and caregivers with 42.1 ± 4.4% and 38.5 ± 6.5%, respectively. A total of 45.2% of beneficiaries and 61.1% of caregivers had their carbohydrate intake within the recommended range. Fiber intake was well below the recommendations (25 g/day) in all groups. Across all levels of care, lower micronutrient intake for pantothenic acid, biotin, folate, potassium, magnesium, copper, selenium, and iodine was observed. Based on the current results, the development and implementation of nutritional guidelines may be targeted to specific populations and nutrient intakes.
Topics: Humans; Caregivers; Prospective Studies; Diet; Energy Intake; Mental Disorders
PubMed: 38201972
DOI: 10.3390/nu16010143 -
Food & Nutrition Research 2023Pantothenic acid, also referred to as vitamin B, is a water-soluble vitamin that has essential functions in the body as a component of coenzyme A (CoA) and acyl carrier... (Review)
Review
Pantothenic acid, also referred to as vitamin B, is a water-soluble vitamin that has essential functions in the body as a component of coenzyme A (CoA) and acyl carrier protein (ACP). It is widely distributed in animal and plant-source foods. Nutritional deficiency of pantothenic acid is rare and toxicity negligible. Information on pantothenic acid intakes in the Nordic countries is limited and biomarker data from Nordic and Baltic populations is missing. Due to a lack of data, no dietary reference values (DRVs) were given for pantothenic acid in the Nordic Nutrition Recommendations (NNR) since 2012. The aim of this scoping review was to examine recent evidence relevant for updating the DRVs for NNR2023. Scientific literature since 2012 on associations of pantothenic acid with health-related issues in Nordic and Baltic countries was searched. No health concerns related to pantothenic acid were identified.
PubMed: 38187802
DOI: 10.29219/fnr.v67.10255 -
Skin Research and Technology : Official... Jan 2024Sensitive skin is a common condition affecting a significant proportion of the population, and there is a growing demand for effective and safe management.
BACKGROUND
Sensitive skin is a common condition affecting a significant proportion of the population, and there is a growing demand for effective and safe management.
AIM
To evaluate the efficacy and safety of a cream containing panthenol, prebiotics, and probiotic lysate as an optimal care for facial sensitive skin.
METHODS
A total of 110 participants (64 in group A and 46 in group B) with facial sensitive skin applied the cream twice daily for 28 days. Group A evaluated their sensitive skin, product efficacy, and product use experience at D0 (15 min), D1, D14, and D28. In group B, skin barrier function-related indicators were measured at baseline and on D1, D7, D14, and D28. Dermatologists evaluated tolerance for all participants.
RESULTS
After 28 days of use, in group A, 100% of participants reported mildness and comfort with product use. Participants demonstrated significant improvements in skin barrier function-related indicators, including increased stratum corneum moisture content, reduced erythema index, elevated sebum content, decreased trans-epidermal water loss, and diminished skin redness parameter a* value (all p < 0.05). Dermatologist evaluations revealed excellent tolerance among all participants.
CONCLUSION
The panthenol-enriched cream with prebiotics and probiotic lysate exhibited substantial clinical efficacy in ameliorating facial sensitive skin conditions, coupled with a high safety profile.
Topics: Humans; Prebiotics; Probiotics; Pantothenic Acid; Facial Dermatoses; Emollients
PubMed: 38186043
DOI: 10.1111/srt.13540 -
Yakugaku Zasshi : Journal of the... 2024The genus Nocardia comprises gram-positive bacteria, most of which are pathogenic and cause opportunistic infections of the lungs, skin, and brain in humans. Based on a...
The genus Nocardia comprises gram-positive bacteria, most of which are pathogenic and cause opportunistic infections of the lungs, skin, and brain in humans. Based on a collaboration study with the Medical Mycology Research Center, Chiba University, we focused on Nocardia actinomycetes as a new natural-product resource. First, by culturing (monoculture) Nocardia in various media, we isolated a new aminocyclitol nabscessin A from Nocardia abscessus IFM10029 and a new γ-lactone inohanalactone from Nocardia inohanaensis IFM0092. On the other hand, by imitating the state in which the genus Nocardia actinomycete infects animal cells and culturing the genus in the presence of animal cells (coculture), this genus was expected to produce new compounds through interactions with the animal cells. Using mouse macrophage-like cells (J774.1) as animal cells, a new pantothenic acid amide derivative and a cyclic peptide, nocarjamide, with Wnt signal activation activity were isolated from Nocardia tenerifensis IFM10554 strain.
Topics: Animals; Mice; Actinobacteria; Actinomyces; Biological Products; Nocardia; Phylogeny
PubMed: 38171791
DOI: 10.1248/yakushi.23-00161-3 -
Chemistry & Biodiversity Feb 2024Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive cartilage and bone erosion. This work aimed to evaluate the metabolomic profile of...
Inflammatory mediators, oxidative stress and genetic disturbance in rheumatoid arthritis rats supported by alfalfa seeds metabolomic constituents via blocking interleukin-1receptor.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive cartilage and bone erosion. This work aimed to evaluate the metabolomic profile of Medicago sativa L. (MS) (alfalfa) seeds and explore its therapeutic impact against RA in rats. Arthritis was induced by complete Freund's adjuvant (CFA) and its severity was assessed by the arthritis index. Treatment with MS seeds butanol fraction and interlukin-1 receptor antagonist (IL-1RA) were evaluated through measuring interlukin-1 receptor (IL-1R) type 1 gene expression, interlukin-1 beta (IL-1β), oxidative stress markers, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), caspase-3 (Cas-3), intracellular adhesion molecule-1 (ICAM-1), DNA fragmentation, and chromosomal damage. Total phenolics/ flavonoids content in the ethyl acetate, butanol fraction and crude extract of MS seeds were estimated. The major identified compounds were Quercetin, Trans-taxifolin, Gallic acid, 7,4'-Dihydroxyflavone, Cinnamic acid, Kudzusaponin SA4, Isorhamnetin 3-O-beta-D-2'',3'',4''-triacetylglucopyranoside, Apigenin, 5,7,4'-Trihydroxy-3'-methoxyflavone, Desmethylxanthohumol, Pantothenic acid, Soyasapogenol E, Malvidin, Helilandin B, Stigmasterol, and Wairol. Treatment with MS seeds butanol fraction and IL-1RA enhanced all the biochemical parameters and the histopathological features of the ankle joint. In conclusion, Trans-taxifolin was isolated for the first time from the genus Medicago. MS butanol fraction seeds extract and IL-1 RA were considered as anti-rheumatic agents.
Topics: Rats; Animals; Plant Extracts; Medicago sativa; Anti-Inflammatory Agents; Phytotherapy; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Arthritis, Experimental; Arthritis, Rheumatoid; Interleukins; Tumor Necrosis Factor-alpha; Oxidative Stress; Butanols; Cytokines
PubMed: 38158718
DOI: 10.1002/cbdv.202301653 -
Journal of Ethnopharmacology Mar 2024PuRenDan (PRD) is a traditional Chinese medicine formula comprising five herbs that have been traditionally used to treat type 2 diabetes mellitus (T2DM). While PRD has...
ETHNOPHARMACOLOGICAL RELEVANCE
PuRenDan (PRD) is a traditional Chinese medicine formula comprising five herbs that have been traditionally used to treat type 2 diabetes mellitus (T2DM). While PRD has been shown to be effective in treating T2DM in clinical and animal studies, the mechanisms by which it works on the gut microbiome and metabolites related to T2DM are not well understood.
AIM OF THE STUDY
The objective of this study was to partially elucidate the mechanism of PRD in treating T2DM through analyses of the gut microbiota metagenome and metabolome.
MATERIALS AND METHODS
Sprague-Dawley rats were fed high-fat diets (HFDs) and injected with low-dose streptozotocin (STZ) to replicate T2DM models. Then the therapeutic effects of PRD were evaluated by measuring clinical markers such as blood glucose, insulin resistance (IR), lipid metabolism biomarkers (total cholesterol, low-density lipoprotein, non-esterified fatty acids, and triglycerides), and inflammatory factors (tumor necrosis factor alpha, interleukin-6 [IL-6], interferon gamma, and IL-1β). Colon contents were collected, and metagenomics, combined with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry metabolic profiling, was performed to evaluate the effects of T2DM and PRD on gut microbiota and its metabolites in rats. Spearman analysis was used to calculate the correlation coefficient among different microbiota, clinical indices, and metabolites.
RESULTS
PRD exhibited significant improvement in blood glucose and IR, and reduced serum levels of lipid metabolism biomarkers and inflammatory factors. Moreover, the diversity and abundance of gut microbiota undergo significant changes in rats with T2DM that PRD was able to reverse. The gut microbiota associated with T2DM including Rickettsiaceae bacterium 4572_127, Psychrobacter pasteurii, Parabacteroides sp. CAG409, and Paludibacter propionicigenes were identified. The gut microbiota most closely related to PRD were Prevotella sp. 10(H), Parabacteroides sp. SN4, Flavobacteriales bacterium, Bacteroides massiliensis, Alistipes indistinctus, and Ruminococcus flavefaciens. Additionally, PRD regulated the levels of gut microbiota metabolites including pantothenic acid, 1-Methylhistamine, and 1-Methylhistidine; these affected metabolites were involved in pantothenate and coenzyme A biosynthesis, histidine metabolism, and secondary bile acid biosynthesis. Correlation analysis illustrated a close relationship among gut microbiota, its metabolites, and T2DM-related indexes.
CONCLUSION
Our study provides insights into the gut microbiota and its metabolites of PRD therapy for T2DM. It clarifies the role of gut microbiota and the metabolites in the pathogenesis of T2DM, highlighting the potential of PRD for the treatment of this disease.
Topics: Rats; Animals; Diabetes Mellitus, Type 2; Rats, Sprague-Dawley; Gastrointestinal Microbiome; Blood Glucose; Bacteria; Insulin Resistance; Biomarkers
PubMed: 38147943
DOI: 10.1016/j.jep.2023.117627 -
Foods (Basel, Switzerland) Dec 2023L-aspartate α-decarboxylase (ADC) is a pyruvoyl-dependent decarboxylase that catalyzes the conversion of L-aspartate to β-alanine in the pantothenate pathway. The...
L-aspartate α-decarboxylase (ADC) is a pyruvoyl-dependent decarboxylase that catalyzes the conversion of L-aspartate to β-alanine in the pantothenate pathway. The enzyme has been extensively used in the biosynthesis of β-alanine and D-pantothenic acid. However, the broad application of ADCs is hindered by low specific activity. To address this issue, we explored 412 sequences and discovered a novel ADC from (CjADC). CjADC exhibited specific activity of 10.7 U/mg and Km of 3.6 mM, which were better than the commonly used ADC from . CjADC was then engineered leveraging structure-guided evolution and generated a mutant, C26V/I88M/Y90F/R3V. The specific activity of the mutant is 28.8 U/mg, which is the highest among the unknown ADCs. Furthermore, the mutant displayed lower Km than the wild-type enzyme. Moreover, we revealed that the introduced mutations increased the structural stability of the mutant by promoting the frequency of hydrogen-bond formation and creating a more hydrophobic region around the active center, thereby facilitating the binding of L-aspartate to the active center and stabilizing the substrate orientation. Finally, the whole-cell bioconversion showed that C26V/I88M/Y90F/R3V completely transformed 1-molar L-aspartate in 12 h and produced 88.6 g/L β-alanine. Our study not only identified a high-performance ADC but also established a research framework for rapidly screening novel enzymes using a protein database.
PubMed: 38137227
DOI: 10.3390/foods12244423 -
Bioresource Technology Feb 2024Brewer's spent grain (BSG) is a main byproduct of the beer industry. BSG is rich in a variety of nutrients, and the search for its effective, high-value utilization is...
Brewer's spent grain (BSG) is a main byproduct of the beer industry. BSG is rich in a variety of nutrients, and the search for its effective, high-value utilization is ongoing. Environmental probiotic factor γ-PGA was produced by fermenting Bacillus subtilis with BSG substrate and the fermenting grain components were analyzed. The γ-PGA yield reached 31.58 ± 0.21 g/kg of BSG. Gas chromatography-mass spectrometry and non-targeted metabolomics analyses revealed 73 new volatile substances in the fermenting grains. Furthermore, 2,376 metabolites were upregulated after fermentation and several components were beneficial for plant growth and development (such as ectoine, acetyl eugenol, L-phenylalanine, niacin, isoprene, pantothenic acid, dopamine, glycine, proline, jasmonic acid, etc). These results show that it is possible to synthesize adequate amounts of γ-PGA for use as a functional fertilizer.
Topics: Fermentation; Fertilizers; Polyglutamic Acid; Edible Grain
PubMed: 38122994
DOI: 10.1016/j.biortech.2023.130216