Fumarate Research Articles

Investigation of the Molecular Mechanism of Asthma in Meishan Pigs Using Multi-Omics Analysis

Asthma has been extensively studied in humans and animals, but the molecular mechanisms underlying asthma in Meishan pigs, a breed with distinct genetic and physiological characteristics, remain elusive. Understanding these mechanisms could provide insights into veterinary medicine and human asthma research. We investigated asthma pathogenesis in Meishan pigs through transcriptomic and metabolomic analyses of blood samples taken during autumn and winter. Asthma in Meishan pigs is related to inflammation, mitochondrial oxidative phosphorylation, and tricarboxylic acid (TCA) cycle disorders. Related genes include CXCL10, CCL8, CCL22, CCL21, OLR1, and ACKR1, while metabolites include succinic acid, riboflavin-5-phosphate, and fumaric acid. Transcriptomic sequencing was performed on panting and normal Meishan pigs, and differentially expressed genes underwent functional enrichment screening. Metabolomic analysis revealed differential metabolites and pathways between groups. Combined analyses indicated that lung inflammation is influenced by genetic, allergenic, and environmental factors disrupting oxidative phosphorylation in lung mitochondria, affecting the TCA cycle. Mitochondrial reactive oxygen species, glutathione S-transferases, arginase 1 and RORC in immune regulation, the Notch pathway, YPEL4 in cell proliferation, and MARCKS in airway mucus secretion play roles in asthma pathogenesis. This study highlights that many cytokines and signaling pathways contribute to asthma. Further studies are needed to elucidate their complex interactions.

Drug Property Optimization: Design, Synthesis, and Characterization of Novel Pharmaceutical Salts and Cocrystal-Salt of Lumefantrine.

Lumefantrine (LMF) is a low-solubility antimalarial drug that cures acute, uncomplicated malaria. It exerts its pharmacological effects against erythrocytic stages of Plasmodium spp. and prevents malaria pathogens from producing nucleic acid and protein, thereby eliminating the parasites. Modifying the structure of a drug through the formation of a pharmaceutical cocrystal or salt presents an avenue through which its physicochemical properties can be optimized. In this work, we report the design/synthesis and solid-state characterization of four new salts and cocrystal-salt forms of LMF; an LMF-ADP salt, monoclinic space group P21/n; an LMF-FUM cocrystal-salt, monoclinic space group P21/c; an LMF-TAR solvate salt, monoclinic space group P21/n; and an LMF-SUC salt, triclinic, space group P1̅ (ADP, dianion of adipic acid; FUM, monoanion of fumaric acid; TAR, dianion of tartaric acid; SUC, dianion of succinic acid). These salts can be obtained by solution as well as by mechanochemical cocrystallization methods. The multicomponent systems gain their stability from hydrogen and partial ionic bonding interactions (N-H···O, O-H···O, N+-H···O-, and O-H+···O-) originating from both the dibutyl ammonium (N+-H) site and the alcohol hydroxyl (-OH) site of LMF toward the carboxylate (-C(O-)═O) functional groups of the coformer anions. SCXRD indicates for LMF-ADP, LMF-TAR, and LMF-SUC complete transfer of all carboxylic acid protons (H+) toward the LMF nitrogen, while for LMF-FUM, one of the protons is transferred (leaving a hydrofumarate monoanion). Using salicylic and acetylsalicylic acids as coformers yielded coamorphous solids. Solid-state characterization using powder X-ray diffraction (XRD) and thermal techniques (DSC and TGA) support and confirm the structures obtained from single-crystal XRD. LMF-ADP and LMF-FUM present superior stability under standard conditions (40 ± 2 °C, 75 ± 5% RH, and 3 months) compared to the amorphous samples and the other two salts. LMF-SUC showed poor thermal stability by DSC/TGA, and powder XRD patterns for LMF-TAR showed substantial change after the 3-month stability test. Finally, the calculated equilibrium solubilities for the cocrystal salts indicate an increase of more than twofold compared to LMF's solubility.

Metabolome and RNA-seq reveal discrepant metabolism and secretory metabolism profile in skeletal muscle between obese and lean pigs at different ages.

Metabolites and metabolism-related gene expression profiles in skeletal muscle change dramatically under obesity, aging and metabolic disease. Since obese and lean pigs are ideal models for metabolic research. Here, we compared metabolome and transcriptome of Longissimus dorsi (LD) muscle between Taoyuan black (TB, obese) and Duroc (lean) pigs at different ages. We defined the "window phase" of intramuscular fat (IMF) deposition in TB pig, which has significantly higher IMF than Duroc pig. Our results displayed discrepant lipid composition and different expression genes (DEGs) enriched in lipid metabolism, and both metabolome and transcriptome analyses revealed stronger energy expenditure and more active amino acid and protein metabolism in Duroc pig. 10 up- and 51 down-regulated biomarker metabolites with age- and breed-specificity were identified. Potential secretory metabolites, including organic acid (fumaric acid, succinate, malic acid, and gamma-aminobutyric acid), amino acid (L-lysine, and L-glutamic acid), lipid (2-hydroxyisovaleric acid, and L-carnitine) were demonstrated a significant correlation with IMF deposition. Our research highlights the huge difference of metabolic spectrum in skeletal muscle between obese and lean model and muscle-derived secretory metabolites might act as an ambassador of intercellular communication to regulate systematic metabolism.

Managing negative linear compressibility and thermal expansion through steric hindrance: a case study of 1,2-bis(4'-pyridyl)ethane cocrystals.

Multicomponent crystals have great scientific potential because of their amenability to crystal engineering in terms of composition and structure, and hence their properties can be easily modified. More and more research areas are employing the design of multicomponent materials to improve the known or induce novel physicochemical properties of crystals, and recently they have been explored as materials with abnormal pressure behaviour. The cocrystal of 1,2-bis(4'-pyridyl)ethane and fumaric acid (ETYFUM) exhibits a negative linear compressibility behaviour comparable to that of framework and metal-containing materials, but overcomes many of their deficiencies restricting their use. Herein ETYFUM was investigated at low temperature to reveal negative thermal expansion behaviour. Additionally, a cocrystal isostructural with ETYFUM, based on 1,2-bis(4'-pyridyl)ethane and succinic acid (ETYSUC), was exposed to high pressure and low temperature, showing that its behaviour is similar in nature to that of ETYFUM, but significantly differs in the magnitude of both effects. It was revealed that the minor structural difference between the acid molecules does not significantly affect the packing under ambient conditions, but has far-reaching consequences when it comes to the deformation of the structure when exposed to external stimuli.

Current Perspectives in Detection of Bioactive Compounds From Costus spicatus Through GC–MS and LC‐MS/MS: Antioxidant Properties and In Silico Analysis for Industrial Applications

Members of the Costus genus are the conventional medicinal plants used in the therapeutic management of numerous ailments, especially for their antioxidant and pharmacological activities. The crude extract of Costus spicatus was profiled using high‐resolution GC–MS and LC‐MS/MS techniques to determine possible bioactive compounds that are vital to the antioxidant activity. A total of 52 and 63 bioactive compounds have been detected in GC–MS chromatograms using different solvents (methanol and ethanol) in C. spicatus leaf extracts, representing the presence of certain bioactive compounds. The identified bioactive compounds in both extracts which exhibit neuroprotective effects have been confirmed through various literature studies. They are cholestan‐3‐amine, loliolide, stigmasterol and methylprednisolone acetate, succinimide, fumaric acid, beta‐tocopherol and gamma‐tocopherol. The aqueous extract possessed the highest antioxidant activity for DPPH scavenging activity and lipid peroxidation inhibition assays, whereas the alcoholic aqueous extract showed superior efficacy for hydroxyl radical scavenging activity. In this study, we performed molecular docking and found that four compounds exhibited promising binding affinities with predicted binding sites on alpha‐synuclein. Notably, Androsta [17‐16‐b] furan‐5′‐imine, 4′‐methylene‐3‐methoxy‐N‐cyclohexyl‐ showed the highest docking interaction score of −7.4, indicating a strong binding affinity. These findings, combined with the presence of bioactive components in the crude extract of C. spicatus, suggest that this plant may possess neuroprotective properties, warranting further investigation for potential industrial applications in the development of neuroprotective agents.

Depicting polymorphism in eutectic mixtures

The current investigation reveals the presence of polymorphism within linezolid eutectic mixtures containing syringic acid, fumaric acid, and isonicotinamide. Linezolid was combined with the said coformers through co-grinding in 1:1 stoichiometric ratios to produce binary mixtures. Through techniques such as differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy, the eutectic nature of these mixtures was confirmed. Polymorphism was identified further through the emergence of an exothermic event positioned between the two melting endotherms in DSC thermograms. This endo-exo-endo transition signifies the thermally-induced polymorphic transformation occurring within the eutectic mixtures. The observed behavior was validated through real-time visual analysis using hot-stage microscopy analysis (HSM). Utilizing PXRD data, quantitative phase analysis (QPA) was employed to determine the weight fractions of individual components in various eutectic polymorphs, yielding reliable outcomes. The morphological characteristics and surface alterations of eutectic polymorphs were scrutinized via scanning electron microscopy (SEM). Moreover, eutectic polymorphs formed by the combination of linezolid and isonicotinamide demonstrated fivefold increase in aqueous solubility and a fourfold faster intrinsic dissolution rate (IDR) compared to marketed linezolid.

Integration of transcriptomics and metabolomics reveals the mechanism of Glycyrrhizae Radix Et Rhizoma extract inhibiting CCL5 in the treatment of acute pharyngitis.

Acute pharyngitis (AP) is a common condition marked by inflammation of the oropharynx, which can lead to severe throat swelling, breathing difficulties, and even suffocation, significantly impacting quality of life. Despite the beneficial anti-inflammatory activity of Glycyrrhizae Radix Et Rhizoma (GRER) and Isoliquiritigenin (ISL), their pharmacological mechanisms against AP remain unclear. This study explores the mechanisms by which GRER treats AP, utilizing both transcriptomics and metabolomics approaches. We identified the chemical components of GRER and those that enter the bloodstream using UPLC-MS/MS. Based on15 % ammonia-induced AP model, this study integrates transcriptomics and metabolomics to investigate the mechanism of GRER and ISL in the AP treatment. The results indicated that GRER has significantly protective and anti-inflammatory effects against AP. Our analysis identified 144 components of GRER in vitro and 17 components in vivo. Network pharmacology and quantitative analysis highlighted ISL as a key active ingredient responsible for GRER's anti-AP effects. Transcriptomics and metabolomics results indicate that GRER and its active ingredient ISL exert therapeutic effects on AP by inhibiting the expression of CCL5 in pharyngeal tissue, thereby downregulating the levels of pro-inflammatory metabolites malic acid and fumaric acid in the tricarboxylic acid (TCA) cycle pathway. The data in this article demonstrated that GRER and ISL has significantly anti-inflammatory effects and protective effects for AP by regulating CCL5 expression to reduce the levels of pro-inflammatory metabolites within TCA cycle pathway. It provides a scientific basis for prevention and treatment of AP.

A multi-levels analysis to evaluate the toxicity of microplastics on aquatic insects: a case study with damselfly larvae (Ischnura elegans)

Microplastic (MP) pollution prevalent in freshwater environments and jeopardizes the organisms living there. Dozens of studies have been conducted to investigate the harmful effects of microplastics on organisms. However, the most diverse and sensitive aquatic insects are often overlooked, also there is a lack of a comprehensive research exploring the toxicity of microplastics. Here, taking the damselfly larvae (Ischnura elegans) as the subject, we investigated the effects of different concentration levels of polystyrene microplastics (PS MPs) on their physiological characters, behavioristics, metabolomics and transcriptomics, as well as gut microbiome. The results showed that the PS MPs had no significant effects on the body weight and survival rate, but led to behavioral inhibition. Furthermore, expression levels of some metabolites altered, such as nicotinic acid, fumaric acid, and stearic acid. Meanwhile, the pathways related to oxidative phosphorylation and carbon metabolism were upregulated at the transcriptomic level. Moreover, there was a modification of the gut microbial community, with an increase in species richness but a shift towards potentially harmful bacteria. Our findings suggested that exposure to PS MPs affected the overall health of damselfly larvae. Therefore, effective management of MPs to minimize their environmental input is crucial in reducing health risks to aquatic organisms.

Evaluating the potential of Acinetobacter calcoaceticus in alleviation of aluminium stress in Triticum aestivum.

Soil contamination with toxic heavy metals [such as aluminum (Al)] is becoming a serious global problem due to the rapid development of the social economy. Although plant growth-promoting rhizo-bacteria (PGPR) are the major protectants to alleviate metal toxicity, the study of these bacteria to ameliorate the toxic effects of Al is limited. Therefore, the present study was conducted to investigate the combined effects of different levels of Acinetobacter calcoaceticus (5ppm and 10ppm) of accession number of MT123456 on plant growth and biomass, photosynthetic pigments, gas exchange attributes, oxidative stress and response of antioxidant compounds (enzymatic and nonenzymatic), and their specific gene expression, sugars, nutritional status of the plant, organic acid exudation pattern and Al accumulation from the different parts of the plants, which was spiked with different levels of Al [0µM (i.e., no Al), 50µM, and 100µM] using aluminum sulfate [Al2(SO4)3] in wheat (Triticum aestivum L.). Results from the present study revealed that the Al toxicity induced a substantial decreased in shoot length, root length, number of leaves, leaf area, shoot fresh weight, root fresh weight, shoot dry weight, root dry weight, chlorophyll-a, chlorophyll-b, total chlorophyll, carotenoid content, net photosynthesis, stomatal conductance, transpiration rate, soluble sugar, reducing sugar, non-reducing sugar contents, calcium (Ca2+), magnesium (Mg2+), iron (Fe2+), and phosphorus (P) contents in the roots and shoots of the plants. In contrast, increasing levels of Al in the soil signifcantly (P < 0.05) increased Al concentration in the roots and shoots of the plants, phenolic content, malondialdehyde (MDA), hydrogen peroxide (H2O2), electrolyte leakage (EL), fumaric acid, acetic acid, citric acid, formic acid, malic acid, oxalic acid contents in the roots of the plants. Although, the activities of enzymatic antioxidants such as superoxidase dismutase, peroxidase, catalase, ascorbate peroxidase and their specific gene expression in the roots and shoots of the plants and non-enzymatic such as phenolic, favonoid, ascorbic acid, and anthocyanin contents were initially increased with the exposure of 50µM Al, but decreased by the increasing the Al concentration 100µM in the soil. Addition of A. calcoaceticus into the soil signifcantly alleviated Al toxicity effects on T. aestivum by improving photosynthetic capacity and ultimately plant growth. Increased activities of antioxidant enzymes in A. calcoaceticus-treated plants seem to play a role in capturing stress-induced reactive oxygen species as was evident from lower levels of MDA, H2O2, MDA, and EL in A. calcoaceticus-treated plants. Research findings, therefore, suggested that A. calcoaceticus application can ameliorate Al toxicity in T. aestivum seedlings and resulted in improved plant growth and composition under metal stress as depicted by balanced exudation of organic acids.

Atmospheric implications of fumaric acid - water binary clusters

Atmospheric implications of fumaric acid - water binary clusters

In-situ reconstructed prism-like CuO on copper foam assisted by fumaric acid for enhanced electrochemical nitrate reduction reaction

In-situ reconstructed prism-like CuO on copper foam assisted by fumaric acid for enhanced electrochemical nitrate reduction reaction

DFT and molecular docking research on the effects of lichen metabolites

Breast cancer remains a significant public health problem worldwide and requires the investigation of new treatment methods. Lichens, symbiotic organisms rich in bioactive compounds, have emerged as promising sources of natural anticancer agents. This study investigates the anticancer effects of lichen metabolites derived from Xanthoparmelia wyomingica on breast cancer cell lines MCF-7 and MDA-MB231. High-performance liquid chromatography (HPLC) was used to measure specific lichen acids in the extract; this revealed the presence of Gyrophoric acid (GA), Norstictic acid (NA), Protocetraric acid (PA), Stictic acid (SA), and Usnic acid (UA). Cytotoxicity analysis showed significant reductions in cell viability, particularly in the MDA-MB231 cell line, with IC50 values ranging from 21.67 to 36.71 µg/mL. Molecular docking studies elucidated the interaction mechanisms between these metabolites and target proteins, highlighting NA as the most promising compound with the lowest binding energy (−9.5 kcal/mol) and inhibition constant (0.108755 μM). ADMET analysis of the molecules was then performed. Molecular electrostatic potential (MEP) and HOMO-LUMO analysis provided further information about the reactivity and electron distribution of the compounds. This study has the potential to provide novel therapeutic agents for breast cancer to tackle the increasing resistance to conventional therapies. Lichen metabolites enable the development of effective therapies in targeting aggressive subtypes such as triple-negative breast cancer with limited treatment options. This research highlights the anticancer properties of lichen metabolites and their potential in the development of innovative strategies for breast cancer treatment. The findings offer a promising avenue to address the urgent need for effective therapies in oncology.

Psoriasis treatments in the stabilization of atherosclerosis: a systematic review

Abstract This systematic review explores the relationship between achieving minimal disease activity in psoriasis and the progression of atherosclerosis. It investigates how biologic therapies and other treatments impact atherosclerosis markers, offering insights into therapeutic strategies. A comprehensive search of PubMed, Embase, and Web of Science was conducted from January 1, 2000, to April 1, 2023, using terms such as psoriasis, psoriatic arthritis, atherosclerosis, biologic therapy, vascular stiffness, carotid intima-media thickness (CIMT), and coronary computed tomography angiography (CCTA). Eligible studies were those involving human subjects over 18, written in English, that provided quantitative atherosclerosis markers, including CIMT, CCTA, arterial pulse wave velocity (aPWV), fat attenuation index (FAI), and augmentation index (Aix). From an initial pool of 217 studies, 21 were included, grouped by treatments, including TNF-α inhibitors, IL-12/23 inhibitors, IL-17 inhibitors, DMARDs, phototherapy, and fumaric acid esters. The review found that TNF-α inhibitors significantly improved atherosclerosis markers such as CIMT, aPWV, FAI, and C-reactive protein (CRP), with reductions in these markers compared to no treatment, phototherapy, and IL-12/23 inhibitors. Additionally, IL-17 inhibitors demonstrated similar reductions in FAI compared to TNF-α inhibitors but showed a greater effect in reducing non-calcified plaque burden (12% vs. 5% for TNF-α inhibitors, p &lt; 0.001) and also decreased CRP levels. Fumaric acid improved cholesterol metabolism (p &lt; 0.04), and TNF-α inhibitors enhanced endothelial function (p &lt; 0.01). Mixed results were observed when compared to DMARDs, indicating that patient-specific factors should guide treatment choices. In conclusion, TNF-α inhibitors are highly effective in reducing atherosclerosis progression in psoriasis patients, consistently improving vascular health markers like CIMT, aPWV, FAI, and CRP. IL-17 inhibitors also show significant efficacy, particularly in reducing non-calcified plaque burden, making them a valuable alternative to TNF-α inhibitors. Fumaric acid’s role in cholesterol metabolism suggests its potential in combination therapies. These findings support integrating TNF-α and IL-17 inhibitors into treatment protocols for psoriasis patients with comorbid atherosclerosis, improving cardiovascular outcomes.

Urinary Metabolite Profiles of Participants with Overweight and Obesity Prescribed a Weight Loss High Fruit and Vegetable Diet: A Single Arm Intervention Study.

Thus far, no studies have examined the relationship between fruit and vegetable (F and V) intake, urinary metabolite quantities, and weight change. Therefore, the aim of the current study was to explore changes in urinary metabolomic profiles during and after a 10-week weight loss intervention where participants were prescribed a high F and V diet (7 servings daily). Adults with overweight and obesity (n = 34) received medical nutrition therapy counselling to increase their F and V intakes to national targets (7 servings a day). Data collection included weight, dietary intake, and urine samples at baseline at week 2 and week 10. Urinary metabolite profiles were quantified using 1H NMR spectroscopy. Machine learning statistical approaches were employed to identify novel urine-based metabolite biomarkers associated with high F and V diet patterns at weeks 2 and 10. Metabolic changes appearing in urine in response to diet were quantified using Metabolite Set Enrichment Analysis (MSEA). Energy intake was significantly lower (p = 0.02) at week 10 compared with baseline. Total F and V intake was significantly higher at week 2 and week 10 (p < 0.05). In total, 123 urinary metabolites were quantified. At week 10, 21 metabolites showed significant changes relative to baseline. Of these, 11 metabolites also significantly changed at week 2. These overlapping metabolites were acetic acid, dimethylamine, choline, fumaric acid, glutamic acid, L-tyrosine, histidine, succinic acid, uracil, histamine, and 2-hydroxyglutarate. Ridge Classifier and Linear Discriminant Analysis provided best prediction accuracy values of 0.96 when metabolite level of baseline was compared to week 10. Urinary metabolites quantified represent potential candidate biomarkers of high F and V intake, associated with a reduction in energy intake. Further studies are needed to validate these findings in larger population studies.

Ketoconazole-Fumaric Acid Pharmaceutical Cocrystal: From Formulation Design for Bioavailability Improvement to Biocompatibility Testing and Antifungal Efficacy Evaluation.

Development of cocrystals through crystal engineering is a viable strategy to formulate poorly water-soluble active pharmaceutical ingredients as stable crystalline solid forms with enhanced bioavailability. This study presents a controlled cocrystallization process by cooling for the 1:1 cocrystal of Ketoconazole, an antifungal class II drug with the Fumaric acid coformer. This was successfully set up following the meta-stable zone width determination in acetone-water 4:6 (V/V) and pure ethanol. Considering the optimal crystallization data, laboratory scale-up processes were carried out at 1 g batch size, efficiently delivering the cocrystal in high yields up to 90% pure and single phase as revealed by powder X-ray diffraction. Biological assays in vitro showed improved viability and oxidative damage of the cocrystal over Ketoconazole on human dermal fibroblasts and hepatocarcinoma cells; in vivo, on Wistar rats, the cocrystal increased oral Ketoconazole bioavailability with transient minor biochemical transaminases increases and without histological liver alterations. Locally on Balb C mice, it induced no epicutaneuous sensitization. A molecular docking study conducted on sterol 14α-demethylase (CYP51) enzyme from the pathogenic yeast Candida albicans revealed that the cocrystal interacts more efficiently with the enzyme compared to Ketoconazole, indicating that the coformer enhances the binding affinity of the active ingredient.

Non-Targeted Metabolomics Analysis of Small Molecular Metabolites in Refrigerated Goose Breast Meat.

Poultry represents a rich source of multiple nutrients. Refrigeration is commonly employed for poultry preservation, although extended storage duration can adversely affect the meat quality. Current research on this topic has focused on the analysis of biochemical indices in chilled goose meat, with limited information on changes in metabolites that influence the quality of the meat during storage. This study used non-targeted metabolomics and the random forest algorithm to investigate metabolite changes in goose meat over an extended storage period. The results showed a significant change in the composition of the meat as the duration of storage increased, with the identification of 121 distinct metabolites. Further analysis identified 18 metabolites that could be used as indicators of the degradation of carbohydrates, amino acids, nucleotides, and lipids. These metabolites could be used as markers to monitor the deterioration process. These intermediate metabolites tended to be transformed into lower-level products involving pyruvate, acetyl coenzyme A, and fumaric acid, used in the tricarboxylic acid cycle, performing substance transformation. This comprehensive analysis of metabolites provides a valuable reference for monitoring the freshness of goose meat, potentially improving the safety of domestic poultry products.

Efficient calcium fumarate overproduction from xylose and corncob-derived xylose by engineered strains of Aureobasidium pullulans var. Aubasidani DH177

BackgroundXylose from lignocellulose is one of the most abundant and important renewable and green raw materials. It is very important how to efficiently transform xylose into useful bioproducts such as fumaric acid and so on.ResultsIn this study, it was found that the GC1 strain (∆gox, in which the GOX gene encoding glucose oxidase which could transform glucose into gluconic acid was removed) of A. pullulans var. aubasidani DH177 had the high ability to utilize xylose and corncob-derived xylose with CO2 fixation derived from CaCO3 to produce calcium fumarate. Overexpression of the XI gene encoding xylose isomerase, the XK gene encoding xylose kinase and the TKL gene coding for transketolase made the strain TKL-4 produce 73.1 g/L of calcium fumarate from xylose. At the same time, the transcriptional levels of the key ASS gene coding for argininosuccinate synthase and the ASL gene coding for argininosuccinate lyase in the ornithine-urea cycle (OUC) were also obviously enhanced. The results also demonstrated that the TKL-4 strain could produce more calcium fumarate from xylose and corncob-derived xylose than from glucose. During 10-liter fermentation, the TKL-4 strain could produce 88.5 g/L of calcium fumarate from xylose, the productivity was 0.52 g/h/L. Meanwhile, it could yield 85.6 g/L of calcium fumarate from corncob-derived xylose and the productivity was 0.51 g/h/L. During the same fermentation, the TKL-4 strain could transform the mixture containing 75.0 g/L glucose and 45.0 g/L xylose to produce 78.7 ± 1.1 g/L calcium fumarate.ConclusionsThis indicated that the TKL-4 strain constructed in this study indeed could actively transform xylose and corncob-derived xylose into calcium fumarate through the green ways.

A chemoenzymatic cascade for sustainable production of chiral N-arylated aspartic acids from furfural and waste

Both biomass valorization and waste upcycling are important routes to sustain the circular bioeconomy. In this work, we present a chemoenzymatic cascade for selective synthesis of chiral N-arylated aspartic acids from biomass-derived furfural and waste nitrophenols (NPs) by merging robust photo- and electrocatalysis with stereoselective biocatalysis. Concurrent photoelectrocatalytic oxidation of furfural into maleic acid (MA) and fumaric acid (FA) was significantly enhanced by combining catalyst and reaction engineering strategies including identification of a powerful photocatalyst meso-tetra(4-carboxyphenyl)porphyrin, continuous flow technique, enhancing dissolved O2 and paired electrosynthesis. The overall space-time yield (STY) approached 2.8 g L−1 h−1 in a fed-batch process, with the product titer of 28.3 g L−1. Besides, photoelectrosynthesis of MA/FA was effectively fueled by sunlight, with the STY of up to 3.6 g L−1 h−1. Both MA selectivity and yield could be facilely improved to around 89% by reducing the buffer concentrations. Paired electrosynthesis strategy not only resulted in greatly improved MA production at the anode, but also enabled NPs upcycling into value-added aminophenols (APs) at the cathode. The products formed in the two electrode chambers were converted into N-arylated (S)-aspartic acids by a bienzymatic cascade. This work presents a multicatalytic approach for integrating selective biomass valorization and waste upcycling towards sustainable manufacture.

Optimization of Aerobic Synthesis of Fumaric Acid from Glucose by a Recombinant Escherichia coli Strain Functioning in a Whole-Cell Biocatalyst Mode

Biocatalytic synthesis of fumaric acid from glucose by the previously engineered E. coli strain FUM1.0 (pMW119-kgd) (E. coli MG1655 ∆ackA-pta, ∆ldhA, ∆adhE, ∆ptsG, PL-glk, Ptac-galP, ∆fumB, ∆fumAC, poxB::PL-pycABs, pMW119-kgd) was optimized. The maximal yield of the target substance was achieved upon its synthesis through a variant of the tricarboxylic acid cycle mediated by the action of heterologous 2-ketoglutarate decarboxylase. The enhanced expression of the genes encoding components of the succinate dehydrogenase enzymatic complex did not markedly affect the biosynthetic characteristics of the producing strain. A positive effect of decreasing the intracellular ATP supply on the conversion of the carbohydrate substrate into the target product was demonstrated. The activation of the futile cycle of pyruvate–phosphoenolpyruvate–pyruvate due to an increase in the expression of the ppsA gene led to a slight increase in the yield of fumaric acid. Upon uncoupling the H+-ATP synthase complex subunits resulting in ATP formation cessation via oxidative phosphorylation, due to deletion of the atpFH genes, the molar yield of fumaric acid from glucose demonstrated by the strain functioning in the whole-cell biocatalyst mode reached 92%.

Thiabendazole: Fumaric acid as a case study on the salt cocrystal continuum: A local vibrational mode perspective

Cocrystals are of tremendous significance for the pharmaceutical industry, due to their favorable properties when compared to their salt analogs. The ΔpKa rule, commonly used in the identification of a cocrystal, meets shortcomings in the 0 ≤ΔpKa≤ 3 range, where salts and cocrystals ought to emerge. In this project, we probed the salt vs. cocrystal nature, using the strength of hydrogen bondings through the local mode analysis, in the case example of the product formed between thiobendazole and fumaric acid. Moreover, we employed a topological analysis of the electronic density to quantify the covalency of such interactions.