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1.
Appl Microbiol Biotechnol ; 108(1): 278, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558151

RESUMO

The production of succinic acid from corn stover is a promising and sustainable route; however, during the pretreatment stage, byproducts such as organic acids, furan-based compounds, and phenolic compounds generated from corn stover inhibit the microbial fermentation process. Selecting strains that are resistant to stress and utilizing nondetoxified corn stover hydrolysate as a feedstock for succinic acid production could be effective. In this study, A. succinogenes CICC11014 was selected as the original strain, and the stress-resistant strain A. succinogenes M4 was obtained by atmospheric and room temperature plasma (ARTP) mutagenesis and further screening. Compared to the original strain, A. succinogenes M4 exhibited a twofold increase in stress resistance and a 113% increase in succinic acid production when hydrolysate was used as the substrate. By conducting whole-genome resequencing of A. succinogenes M4 and comparing it with the original strain, four nonsynonymous gene mutations and two upstream regions with base losses were identified. KEY POINTS: • A high-stress-resistant strain A. succinogenes M4 was obtained by ARTP mutation •  The production of succinic acid increased by 113% • The mutated genes of A. succinogenes M4 were detected and analyzed.


Assuntos
Actinobacillus , Zea mays , Zea mays/química , Ácido Succínico , Melhoramento Vegetal , Fermentação , Mutação
2.
Appl Microbiol Biotechnol ; 108(1): 293, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592508

RESUMO

Kluyveromyces marxianus has become an attractive non-conventional yeast cell factory due to its advantageous properties such as high thermal tolerance and rapid growth. Succinic acid (SA) is an important platform molecule that has been applied in various industries such as food, material, cosmetics, and pharmaceuticals. SA bioproduction may be compromised by its toxicity. Besides, metabolite-responsive promoters are known to be important for dynamic control of gene transcription. Therefore, studies on global gene transcription under various SA concentrations are of great importance. Here, comparative transcriptome changes of K. marxianus exposed to various concentrations of SA were analyzed. Enrichment and analysis of gene clusters revealed repression of the tricarboxylic acid cycle and glyoxylate cycle, also activation of the glycolysis pathway and genes related to ergosterol synthesis. Based on the analyses, potential SA-responsive promoters were investigated, among which the promoter strength of IMTCP2 and KLMA_50231 increased 43.4% and 154.7% in response to 15 g/L SA. In addition, overexpression of the transcription factors Gcr1, Upc2, and Ndt80 significantly increased growth under SA stress. Our results benefit understanding SA toxicity mechanisms and the development of robust yeast for organic acid production. KEY POINTS: • Global gene transcription of K. marxianus is changed by succinic acid (SA) • Promoter activities of IMTCP2 and KLMA_50123 are regulated by SA • Overexpression of Gcr1, Upc2, and Ndt80 enhanced SA tolerance.


Assuntos
Kluyveromyces , Ácido Succínico , Kluyveromyces/genética , Perfilação da Expressão Gênica , Transcriptoma
3.
FEMS Yeast Res ; 242024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38587863

RESUMO

Previously, we reported an engineered Saccharomyces cerevisiae CEN.PK113-1A derivative able to produce succinic acid (SA) from glycerol with net CO2 fixation. Apart from an engineered glycerol utilization pathway that generates NADH, the strain was equipped with the NADH-dependent reductive branch of the TCA cycle (rTCA) and a heterologous SA exporter. However, the results indicated that a significant amount of carbon still entered the CO2-releasing oxidative TCA cycle. The current study aimed to tune down the flux through the oxidative TCA cycle by targeting the mitochondrial uptake of pyruvate and cytosolic intermediates of the rTCA pathway, as well as the succinate dehydrogenase complex. Thus, we tested the effects of deletions of MPC1, MPC3, OAC1, DIC1, SFC1, and SDH1 on SA production. The highest improvement was achieved by the combined deletion of MPC3 and SDH1. The respective strain produced up to 45.5 g/L of SA, reached a maximum SA yield of 0.66 gSA/gglycerol, and accumulated the lowest amounts of byproducts when cultivated in shake-flasks. Based on the obtained data, we consider a further reduction of mitochondrial import of pyruvate and rTCA intermediates highly attractive. Moreover, the approaches presented in the current study might also be valuable for improving SA production when sugars (instead of glycerol) are the source of carbon.


Assuntos
Saccharomyces cerevisiae , Ácido Succínico , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ácido Succínico/metabolismo , Glicerol/metabolismo , Dióxido de Carbono/metabolismo , NAD/metabolismo , Ácido Pirúvico/metabolismo , Membranas Mitocondriais/metabolismo , Carbono/metabolismo , Engenharia Metabólica/métodos
4.
Int. microbiol ; 27(2): 361-376, Abr. 2024.
Artigo em Inglês | IBECS | ID: ibc-232286

RESUMO

With the increasingly serious problem of phosphorus deficiency in the subtropical zone, chemical fertilizers are widely used. But it pollutes the environment. Phosphorus-solubilizing microorganisms (PSMs) are referred to as a new solution to this problem. We explored the phosphorus-dissolving characteristics of PSB strains isolated from the rhizosphere soil of Torreya grandis to provide a theoretical basis for selecting the strain for managing phosphorus deficiency in subtropical soils and also provides a more sufficient theoretical basis for the utilization of PSMs. From 84 strains, three strains exhibiting high phosphorus solubility and strong IAA producing capacity were selected through a series of experiments. The phosphate-solubilizing capacity of the three selected strains W1, W74, and W83 were 339.78 mg/L, 332.57 mg/L, and 358.61 mg/L, respectively. Furthermore, W1 showed the strongest IAA secreting capacity of 8.62 mg/L, followed by W74 (7.58 mg/L), and W83 (7.59 mg/L). Determination by metabolites, it was observed that these three strains dissolved phosphorus by secreting a large amount of lactic acid, aromatic acid, and succinic acid. The genome of these PSBs were sequenced and annotated in this study. Our results revealed that PSB primarily promotes their metabolic pathway, especially carbon metabolism, to secrete plenty organic acids for dissolving insoluble phosphorus. (AU)


Assuntos
Humanos , Fósforo , Células Produtoras de Anticorpos , Ácido Láctico , Ácido Succínico
5.
Int. microbiol ; 27(2): 505-512, Abr. 2024. graf, tab
Artigo em Inglês | IBECS | ID: ibc-232296

RESUMO

As a consequence of alcoholic fermentation (AF) in wine, several compounds are released by yeasts, and some of them are linked to the general quality and mouthfeel perceptions in wine. However, others, such as succinic acid, act as inhibitors, mainly of malolactic fermentation. Succinic acid is produced by non-Saccharomyces and Saccharomyces yeasts during the initial stages of AF, and the presence of some amino acids such as γ-aminobutyric acid (GABA) and glutamic acid can increase the concentration of succinic acid. However, the influence of these amino acids on succinic acid production has been studied very little to date. In this work, we studied the production of succinic acid by different strains of non-Saccharomyces and Saccharomyces yeasts during AF in synthetic must, and the influence of the addition of GABA or glutamic acid or a combination of both. The results showed that succinic acid can be produced by non-Saccharomyces yeasts with values in the range of 0.2–0.4 g/L. Moreover, the addition of GABA or glutamic acid can increase the concentration of succinic acid produced by some strains to almost 100 mg/L more than the control, while other strains produce less. Consequently, higher succinic acid production by non-Saccharomyces yeast in coinoculated fermentations with S. cerevisiae strains could represent a risk of inhibiting Oenococcus oeni and therefore the MLF.(AU)


Assuntos
Humanos , Ácido Succínico , Ácido Glutâmico , Aminoácidos , Saccharomyces cerevisiae , Vinho/análise , Vinho/microbiologia , Ácido gama-Aminobutírico , Microbiologia , Leveduras , Fermentação
6.
Sci Rep ; 14(1): 8045, 2024 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580674

RESUMO

Silver and titanium-silver nanoparticles have unique properties that make the textile industry progress through the high quality of textiles. Preparation of AgNPs and TiO2-Ag core-shell nanoparticles in different concentrations (0.01% and 0.1% OWF) and applying it to cotton fabrics (Giza 88 and Giza 94) by using succinic acid 5%/SHP as a cross-linking agent. Ultra-violet visible spectroscopy (UV-Vis), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), scanning electron microscopy/energy-dispersive X-ray (SEM-EDX) are tools for AgNPs and TiO2-AgNPs characterization and the treated cotton. The resulting AgNPs and TiO2-AgNPs were added to cotton fabrics at different concentrations. The antimicrobial activities, UV protection, self-cleaning, and the treated fabrics' mechanical characteristics were investigated. Silver nanoparticles and titanium dioxide-silver nanoparticles core-shell were prepared to be used in the treatment of cotton fabrics to improve their UV protection properties, self-cleaning, elongation and strength, as well as the antimicrobial activities to use the produced textiles for medical and laboratory uses and to increase protection for medical workers taking into account the spread of infection. The results demonstrated that a suitable distribution of prepared AgNPs supported the spherical form. Additionally, AgNPs and TiO2-AgNPs have both achieved stability, with values of (- 20.8 mV and - 30 mV, respectively). The synthesized nanoparticles spread and penetrated textiles' surfaces with efficiency. The findings demonstrated the superior UV protection value (UPF 50+) and self-cleaning capabilities of AgNPs and TiO2-AgNPs. In the treatment with 0.01% AgNPs and TiO2-AgNPs, the tensile strength dropped, but the mechanical characteristics were enhanced by raising the concentration to 0.1%. The results of this investigation demonstrated that the cotton fabric treated with TiO2-AgNPs exhibited superior general characteristics when compared to the sample treated only with AgNPs.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Humanos , Prata/química , Fibra de Algodão , Ácido Succínico , Nanopartículas Metálicas/química , Têxteis , Antibacterianos/farmacologia , Antibacterianos/química
7.
Arch Microbiol ; 206(4): 141, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441685

RESUMO

A strictly anaerobic, motile bacterium, designated as strain Ai-910T, was isolated from the sludge of an anaerobic digestion tank in China. Cells were Gram-stain-negative rods. Optimal growth was observed at 38 °C (growth range 25-42 °C), pH 8.5 (growth range 5.5-10.5), and under a NaCl concentration of 0.06% (w/v) (range 0-2.0%). Major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The respiratory quinone was MK-7. Using xylose as the growth substrate, succinate was produced as the fermentation product. Phylogenetic analysis based on the 16 S rRNA gene sequences indicated that strain Ai-910T formed a distinct phylogenetic lineage that reflects a new genus in the family Marinilabiliaceae, sharing high similarities to Alkaliflexus imshenetskii Z-7010T (92.78%), Alkalitalea saponilacus SC/BZ-SP2T (92.51%), and Geofilum rubicundum JAM-BA0501T (92.36%). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain Ai-910T and its phylogenetic neighbors were below 65.27 and 16.90%, respectively, indicating that strain Ai-910T represented a novel species. The average amino acid identity between strain Ai-910T and other related members of the family Marinilabiliaceae were below 69.41%, supporting that strain Ai-910T was a member of a new genus within the family Marinilabiliaceae. Phylogenetic, genomic, and phenotypic analysis revealed that strain Ai-910T was distinguished from other phylogenetic relatives within the family Marinilabiliaceae. The genome size was 3.10 Mbp, and the DNA G + C content of the isolate was 42.8 mol%. Collectively, differences of the phenotypic and phylogenetic features of strain Ai-910T from its close relatives suggest that strain Ai-910T represented a novel species in a new genus of the family Marinilabiliaceae, for which the name Xiashengella succiniciproducens gen. nov., sp. nov. was proposed. The type strain of Xiashengella succiniciproducens is Ai-910T (= CGMCC 1.17893T = KCTC 25,304T).


Assuntos
Bactérias , Ácido Succínico , Anaerobiose , Filogenia , Succinatos , DNA
8.
BMC Gastroenterol ; 24(1): 106, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486162

RESUMO

To investigate the effect of Oncometabolite succinate on colorectal cancer migration and invasion and to initially explore the underlying mechanism.Succinate acid detection kit detected the succinate content in tissues. The growth of colorectal cancer cells was measured by cck-8 assay, wound-healing migration assay and transwell migration and invasion assays, and then explored the level of epithelial-mesenchymal transition (EMT) and STAT3/ p-STAT3 expression by western blot analysis and quantitative real-time PCR for mRNA expression. We found that succinate levels were significantly higher in carcinoma tissues than paracancerous tissues. After succinate treatment, the colorectal cancer cell lines SW480 and HCT116 had enhanced migration and invasion, the expression of biomarkers of EMT was promoted, and significantly increased phosphorylation of STAT3. In vivo experiments also showed that succinate can increase p-STAT3 expression, promote the EMT process, and promote the distant metastasis of colorectal cancer in mice.Succinate promotes EMT through the activation of the transcription factor STAT3, thus promoting the migration and invasion of colorectal cancer.


Assuntos
Neoplasias Colorretais , Animais , Camundongos , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Ácido Succínico , Fosforilação
9.
PLoS Genet ; 20(3): e1011142, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38457455

RESUMO

Succinate is a potent immune signalling molecule that is present in the mammalian gut and within macrophages. Both of these infection niches are colonised by the pathogenic bacterium Salmonella enterica serovar Typhimurium during infection. Succinate is a C4-dicarboyxlate that can serve as a source of carbon for bacteria. When succinate is provided as the sole carbon source for in vitro cultivation, Salmonella and other enteric bacteria exhibit a slow growth rate and a long lag phase. This growth inhibition phenomenon was known to involve the sigma factor RpoS, but the genetic basis of the repression of bacterial succinate utilisation was poorly understood. Here, we use an experimental evolution approach to isolate fast-growing mutants during growth of S. Typhimurium on succinate containing minimal medium. Our approach reveals novel RpoS-independent systems that inhibit succinate utilisation. The CspC RNA binding protein restricts succinate utilisation, an inhibition that is antagonised by high levels of the small regulatory RNA (sRNA) OxyS. We discovered that the Fe-S cluster regulatory protein IscR inhibits succinate utilisation by repressing the C4-dicarboyxlate transporter DctA. Furthermore, the ribose operon repressor RbsR is required for the complete RpoS-driven repression of succinate utilisation, suggesting a novel mechanism of RpoS regulation. Our discoveries shed light on the redundant regulatory systems that tightly regulate the utilisation of succinate. We speculate that the control of central carbon metabolism by multiple regulatory systems in Salmonella governs the infection niche-specific utilisation of succinate.


Assuntos
Proteínas de Bactérias , Ácido Succínico , Animais , Proteínas de Bactérias/metabolismo , Ácido Succínico/metabolismo , Salmonella typhimurium/genética , Succinatos/metabolismo , Carbono/metabolismo , Fator sigma/genética , Fator sigma/metabolismo , Regulação Bacteriana da Expressão Gênica , Mamíferos/metabolismo
10.
Artigo em Russo | MEDLINE | ID: mdl-38529859

RESUMO

The review is devoted to a comparative analysis of the clinical efficacy of the original domestic derivatives of 3-hydroxypyridine and succinic acid (emoxipine, reamberin and mexidol) in comparison with the results of an experimental study of their dopaminergic action. The position that the dopaminomimetic activity of emoxipin, reamberin and mexidol largely determines their anti-ischemic, antihypoxic, insulin-potentiating neuroprotective, nootropic and antidepressant potential has been substantiated. A comparative analysis of the safety profile of emoxipine, reamberin and mexidol was carried out, taking into account potential and real side-effects caused by iatrogenic deviations from the eudopaminergic state. It has been shown that mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), which is simultaneously a derivative of 3-hydroxypyridine and succinic acid, has the best balance of efficacy and safety. A generalized assessment of the available data on the successful use of off-label derivatives of 3-hydroxypyridine and succinic acid indicates the advisability of a significant expansion of indications for their clinical use. The authors resume that the «therapeutic retargeting¼ of emoxipin, reamberin and mexidol (i.e. their use for qualitatively new indications) will contribute to progress in the treatment of socially significant and most common diseases.


Assuntos
Meglumina/análogos & derivados , Succinatos , Ácido Succínico , Humanos , Ácido Succínico/uso terapêutico , Succinatos/uso terapêutico , Picolinas/uso terapêutico , Piridinas/uso terapêutico
11.
Appl Environ Microbiol ; 90(4): e0000824, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38506527

RESUMO

Currently, the L-malic acid titer achieved through Aspergillus niger fermentation reaches 201 g/L, meeting industrial demands satisfactorily. However, the co-presence of structurally similar fumaric acid and succinic acid in fermentation products suggests a theoretical potential for further improvement in L-malic acid production. In the tricarboxylic acid cycle, fumarate reductase mediates the conversion of succinic acid to fumaric acid. Subsequently, fumarase catalyzes the conversion of fumaric acid to L-malic acid. Notably, both enzymatic reactions are reversible. Our investigation revealed that A. niger contains only one mitochondria-located fumarase FumA. Employing CRISPR-Cas9 technology, we performed a replacement of the fumA promoter with a doxycycline-induced promoter Tet. Under non-inducing condition, the conditional strain exhibited increased levels of fumaric acid and succinic acid. It strongly suggests that FumA mainly promotes the flow of fumaric acid to L-malic acid. Furthermore, a promoter PmfsA that is exclusively activated in a fermentation medium by calcium carbonate was identified through RNA-sequencing screening. Utilizing PmfsA to regulate fumA expression led to a 9.0% increase in L-malic acid titer, an 8.75% increase in yield (glucose to L-malic acid), and an 8.86% enhancement in productivity. This research serves as a significant step toward expediting the industrialization of L-malic acid synthesis via biological fermentation. Additionally, it offers valuable insights for the biosynthesis of other organic acids.IMPORTANCEThis study focuses on enhancing L-malic acid synthesis by modifying the tricarboxylic acid cycle within the mitochondria of Aspergillus niger. We emphasize the significant role of fumarase in converting fumaric acid into L-malic acid, enhancing our understanding of metabolic pathways in A. niger. The precise regulation of fumA is highlighted as a key factor in enhancing L-malic acid production. Furthermore, this research introduces a stringent conditional promoter (PmfsA), exclusively activated by CaCO3. The utilization of PmfsA for fumA expression resulted in heightened L-malic acid titers. The progress in metabolic engineering and bioprocess optimization holds promise for expediting industrial L-malic acid synthesis via biological fermentation. Moreover, it carries implications for the biosynthesis of various other organic acids.


Assuntos
Aspergillus niger , Fumarato Hidratase , Fumaratos , Aspergillus niger/genética , Aspergillus niger/metabolismo , Fumarato Hidratase/genética , Fumarato Hidratase/metabolismo , Malatos/metabolismo , Ácido Succínico
12.
Nat Metab ; 6(3): 567-577, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38378996

RESUMO

Uptake of circulating succinate by brown adipose tissue (BAT) and beige fat elevates whole-body energy expenditure, counteracts obesity and antagonizes systemic tissue inflammation in mice. The plasma membrane transporters that facilitate succinate uptake in these adipocytes remain undefined. Here we elucidate a mechanism underlying succinate import into BAT via monocarboxylate transporters (MCTs). We show that succinate transport is strongly dependent on the proportion that is present in the monocarboxylate form. MCTs facilitate monocarboxylate succinate uptake, which is promoted by alkalinization of the cytosol driven by adrenoreceptor stimulation. In brown adipocytes, we show that MCT1 primarily facilitates succinate import. In male mice, we show that both acute pharmacological inhibition of MCT1 and congenital depletion of MCT1 decrease succinate uptake into BAT and consequent catabolism. In sum, we define a mechanism of succinate uptake in BAT that underlies its protective activity in mouse models of metabolic disease.


Assuntos
Adipócitos Marrons , Ácido Succínico , Masculino , Camundongos , Animais , Adipócitos Marrons/metabolismo , Ácido Succínico/metabolismo , Tecido Adiposo Marrom/metabolismo , Transporte Biológico , Proteínas de Membrana Transportadoras/metabolismo
14.
Microb Biotechnol ; 17(2): e14410, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38298109

RESUMO

Although a high titre of malic acid is achieved by filamentous fungi, by-product succinic acid accumulation leads to a low yield of malic acid and is unfavourable for downstream processing. Herein, we conducted a series of metabolic rewiring strategies in a previously constructed Myceliophthora thermophila to successfully improve malate production and abolish succinic acid accumulation. First, a pyruvate carboxylase CgPYC variant with increased activity was obtained using a high-throughput system and introduced to improve malic acid synthesis. Subsequently, shifting metabolic flux to malate synthesis from mitochondrial metabolism by deleing mitochondrial carriers of pyruvate and malate, led to a 53.7% reduction in succinic acid accumulation. The acceleration of importing cytosolic succinic acid into the mitochondria for consumption further decreased succinic acid formation by 53.3%, to 2.12 g/L. Finally, the importer of succinic acid was discovered and used to eliminate by-product accumulation. In total, malic acid production was increased by 26.5%, relative to the start strain JG424, to 85.23 g/L and 89.02 g/L on glucose and Avicel, respectively, in the flasks. In a 5-L fermenter, the titre of malic acid reached 182.7 g/L using glucose and 115.8 g/L using raw corncob, without any by-product accumulation. This study would accelerate the industrial production of biobased malic acid from renewable plant biomass.


Assuntos
Malatos , Sordariales , Ácido Succínico , Ácido Succínico/metabolismo , Malatos/metabolismo , Malato Desidrogenase/metabolismo , Succinatos , Ácido Pirúvico/metabolismo , Glucose/metabolismo
15.
Mol Cell ; 84(5): 955-966.e4, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38325379

RESUMO

SUCNR1 is an auto- and paracrine sensor of the metabolic stress signal succinate. Using unsupervised molecular dynamics (MD) simulations (170.400 ns) and mutagenesis across human, mouse, and rat SUCNR1, we characterize how a five-arginine motif around the extracellular pole of TM-VI determines the initial capture of succinate in the extracellular vestibule (ECV) to either stay or move down to the orthosteric site. Metadynamics demonstrate low-energy succinate binding in both sites, with an energy barrier corresponding to an intermediate stage during which succinate, with an associated water cluster, unlocks the hydrogen-bond-stabilized conformationally constrained extracellular loop (ECL)-2b. Importantly, simultaneous binding of two succinate molecules through either a "sequential" or "bypassing" mode is a frequent endpoint. The mono-carboxylate NF-56-EJ40 antagonist enters SUCNR1 between TM-I and -II and does not unlock ECL-2b. It is proposed that occupancy of both high-affinity sites is required for selective activation of SUCNR1 by high local succinate concentrations.


Assuntos
Receptores Acoplados a Proteínas G , Ácido Succínico , Camundongos , Ratos , Animais , Humanos , Ácido Succínico/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Simulação de Dinâmica Molecular , Succinatos/metabolismo , Estresse Fisiológico
16.
Food Res Int ; 179: 114033, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342553

RESUMO

Elucidating the driving mechanism of microbial community succession during pepper fermentation contributes to establishing efficient fermentation regulation strategies. This study utilized three-generation high-throughput sequencing technology, microbial co-occurrence network analysis, and random forest analysis to reveal microbial community succession processes and driving mechanisms during pepper fermentation. The results showed that more positive correlations than negative correlations were observed among microorganisms, with positive correlation proportions of 60 %, 51.03 %, and 71.43 % between bacteria and bacteria, fungi and fungi, and bacteria and fungi in sipingtou peppers, and 69.23 %, 54.93 %, and 79.44 % in zhudachang peppers, respectively. Microbial interactions, mainly among Weissella hellenica, Lactobacillus plantarum, Hanseniaspora opuntiae, and Kazachstania humillis, could drive bacterial and fungal community succession. Notably, the bacterial community successions during the fermentation of two peppers were similar, showing the transition from Leuconostoc pseudomesenteroides, Lactococcus lactis, Weissella ghanensis to Weissella hellenica and Lactobacillus plantarum. However, the fungal community successions in the two fermented peppers differed significantly, and the differential biomarkers were Dipodascus geotrichum and Kazachstania humillis. Differences in autochthonous microbial composition and inherent constituents brought by pepper varieties resulted in different endogenous environmental changes, mainly in fructose, malic acid, and citric acid. Furthermore, endogenous environmental factors could also drive microbial community succession, with succinic acid, lactic acid, and malic acid being the main potential drivers of bacterial community succession, whereas fructose, glucose, and succinic acid were the main drivers of fungal community succession. These results will provide insights into controlling fermentation processes by raw material combinations, optimization of environmental parameters, and microbial interactions.


Assuntos
Lactobacillus plantarum , Malatos , Microbiota , Saccharomycetales , Weissella , Fermentação , Ácido Succínico , Bactérias/genética , Interações Microbianas , Frutose
17.
Int J Mol Sci ; 25(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38397087

RESUMO

It is well known that in the heart and kidney mitochondria, more than 95% of ATP production is supported by the ß-oxidation of long-chain fatty acids. However, the ß-oxidation of fatty acids by mitochondria has been studied much less than the substrates formed during the catabolism of carbohydrates and amino acids. In the last few decades, several discoveries have been made that are directly related to fatty acid oxidation. In this review, we made an attempt to re-evaluate the ß-oxidation of long-chain fatty acids from the perspectives of new discoveries. The single set of electron transporters of the cardiac mitochondrial respiratory chain is organized into three supercomplexes. Two of them contain complex I, a dimer of complex III, and two dimers of complex IV. The third, smaller supercomplex contains a dimer of complex III and two dimers of complex IV. We also considered other important discoveries. First, the enzymes of the ß-oxidation of fatty acids are physically associated with the respirasome. Second, the ß-oxidation of fatty acids creates the highest level of QH2 and reverses the flow of electrons from QH2 through complex II, reducing fumarate to succinate. Third, ß-oxidation is greatly stimulated in the presence of succinate. We argue that the respirasome is uniquely adapted for the ß-oxidation of fatty acids. The acyl-CoA dehydrogenase complex reduces the membrane's pool of ubiquinone to QH2, which is instantly oxidized by the smaller supercomplex, generating a high energization of mitochondria and reversing the electron flow through complex II, which reverses the electron flow through complex I, increasing the NADH/NAD+ ratio in the matrix. The mitochondrial nicotinamide nucleotide transhydrogenase catalyzes a hydride (H-, a proton plus two electrons) transfer across the inner mitochondrial membrane, reducing the cytosolic pool of NADP(H), thus providing the heart with ATP for muscle contraction and energy and reducing equivalents for the housekeeping processes.


Assuntos
Complexo III da Cadeia de Transporte de Elétrons , Ácidos Graxos , Ácidos Graxos/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Oxirredução , Mitocôndrias Cardíacas/metabolismo , Membranas Mitocondriais/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Ácido Succínico/metabolismo , Succinatos/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Trifosfato de Adenosina/metabolismo
18.
Environ Sci Pollut Res Int ; 31(11): 16819-16831, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38324158

RESUMO

Succinate dehydrogenase inhibitor fungicides (SDHIs) are frequently detected in the marine environment. However, studies on the toxicity of SDHIs to marine organisms, Mytilus coruscus (M. coruscus), are poorly reported. Therefore, the antioxidant activities and metabolomic response of four SDHIs, namely, boscalid (BC), thifluzamide (TF), fluopyram (FO), and bixafen (BIX), to (M. coruscus), were comprehensively investigated. The antioxidant activity of BC and TF was significantly increased (p<0.05), whereas those of FO and BIX were significantly decreased. Furthermore, metabolite discriminations among M. coruscus to four SDHIs were illustrated by an untargeted metabolomics approach. A total of 52, 50, 93, and 129 differential metabolites were obtained for BC, TF, FO, and BIX. KEGG of the different metabolites show that the four SDHIs had differential effects on the metabolic pathways of M. coruscus. The current study demonstrated four SDHIs triggered glucose metabolism, lipid metabolism, tricarboxylic acid cycle, and oxidative phosphorylation processes and caused the disruption of nutrient and energy conversion processes in mussels. Finally, five biomarkers were screened by analyzing common differential metabolites that emerged from the four SDHI exposures, which could be used for risk assessment of marine ecosystem exposure to SDHIs. Our results demonstrated the use of metabolomics to understand the potential mechanisms of toxicity of four SDHIs to mussels and to identify potential targets for future targeted risk assessment.


Assuntos
Benzamidas , Compostos de Bifenilo , Fungicidas Industriais , Mytilus , Niacinamida/análogos & derivados , Piridinas , Animais , Fungicidas Industriais/toxicidade , Succinato Desidrogenase/metabolismo , Antioxidantes , Mytilus/metabolismo , Ácido Succínico , Ecossistema , Succinatos
19.
Phytomedicine ; 125: 155266, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38241917

RESUMO

BACKGROUND: Increasing evidence highlights the involvement of metabolic disorder and calcium influx mediated by transient receptor potential channels in migraine; however, the relationship between these factors in the pathophysiology of migraine remains unknown. Gastrodin is the major component of the traditional Chinese medicine Tianma, which is extensively used in migraine therapy. PURPOSE: Our work aimed to explore the analgesic action of gastrodin and its regulatory mechanisms from a metabolic perspective. METHODS/RESULTS: After being treated with gastrodin, the mice were given nitroglycerin (NTG) to induce migraine. Gastrodin treatment significantly raised the threshold of sensitivity in response to both mechanical and thermal stimulus evidenced by von Frey and hot plate tests, respectively, and decreased total contact numbers in orofacial operant behavioral assessment. We found that the expression of transient receptor potential melastatin 2 (TRPM2) channel was increased in the trigeminal ganglion (TG) of NTG-induced mice, resulting in a sustained Ca2+ influx to trigger migraine pain. The content of succinate, a metabolic biomarker, was elevated in blood samples of migraineurs, as well as in the serum and TG tissue from NTG-induced migraine mice. Calcium imaging assay indicated that succinate insult elevated TRPM2-mediated calcium flux signal in TG neurons. Mechanistically, accumulated succinate upregulated hypoxia inducible factor-1α (HIF-1α) expression and promoted its translocation into nucleus, where HIF-1α enhanced TRPM2 expression through transcriptional induction in TG neurons, evidenced by luciferase reporter measurement. Gastrodin treatment inhibited TRPM2 expression and TRPM2-dependent Ca2+ influx by attenuating succinate accumulation and downstream HIF-1α signaling, and thereby exhibited analgesic effect. CONCLUSION: This work revealed that succinate was a critical metabolic signaling molecule and the key mediator of migraine pain through triggering TRPM2-mediated calcium overload. Gastrodin alleviated NTG-induced migraine-like pain via inhibiting succinate/HIF-1α/TRPM2 signaling pathway in TG neurons. These findings uncovered the anti-migraine effect of gastrodin and its regulatory mechanisms from a metabolic perspective and provided a novel theoretical basis for the analgesic action of gastrodin.


Assuntos
Álcoois Benzílicos , Glucosídeos , Transtornos de Enxaqueca , Canais de Cátion TRPM , Camundongos , Animais , Nitroglicerina/efeitos adversos , Nitroglicerina/metabolismo , Ácido Succínico/efeitos adversos , Ácido Succínico/metabolismo , Cálcio/metabolismo , Canais de Cátion TRPM/efeitos adversos , Canais de Cátion TRPM/metabolismo , Gânglio Trigeminal/metabolismo , Dor/tratamento farmacológico , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/tratamento farmacológico , Transdução de Sinais , Analgésicos/farmacologia
20.
Cell Commun Signal ; 22(1): 82, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291428

RESUMO

BACKGROUND: As a dual-function metabolite, succinate has emerged in cell function and plays a key signaling role in linking mitochondrial function to other cellular functions. Succinate accumulation in the cytoplasm is commonly associated with hypoxia in the microenvironment and immune cell activation. Extracellular succinate released into the microenvironment is considered an inflammatory alarm that can be sensed by its membrane receptor SUCNR1, which boosts proinflammatory responses and acts akin to classical hormones and cytokines. Succinate plays an important role in the development of inflammatory diseases. Whether succinate facilitates the progression of endometriosis (EMs), characterized by chronic inflammation and peritoneal adhesion, is worth exploring. OBJECTIVE: We mimicked the ectopic milieu in vitro and in vivo to evaluate the main source and potential role of succinate in endometriosis. We assessed the molecular and functional effects of succinate on macrophages and peritoneal mesothelial cells in peritoneal cavity. The effect of succinate/SUCNR1 signaling on ectopic endometrial stromal cells (ESCs) was further explored in this study. METHODS: In this study, we used targeted organic acid metabolomics analysis and in vitro assays to assess the potential accumulation of succinate in the peritoneal fluid of EMs patients. We examined its correlation with disease severity, Visual Analogue Scale, and the Endometriosis Fertility Index. Flow cytometry, enzyme linked immunosorbent assay, western blot assay, quantitative real-time PCR, and other molecular biology techniques were used to explore the potential mechanisms. RESULTS: By mimicking the ectopic milieu, we constructed an in vitro co-culture system and found that M1 polarized macrophages and that the peritoneal mesothelial cell line (HMrSV5) mainly released succinate into their microenvironment and activated the succinate receptor (SUCNR1) signal, which further polarized the macrophages and significantly enhanced the invasive survival of ESCs, and the adhesion to the peritoneum. We further investigated the pathological effects of extracellular succinate in vivo using a xenograft mouse models of endometriosis. CONCLUSIONS: Succinate-SUCNR1 signaling facilitates the creation of inflammatory cells and plays a vital role in EMs progression and peritoneal adhesion. Our work on the molecular mechanisms underlying succinate accumulation and function will help elucidate the phenotypic mysteries of pain and infertility in EMs. Video Abstract.


Assuntos
Endometriose , Ácido Succínico , Feminino , Humanos , Animais , Camundongos , Ácido Succínico/metabolismo , Endometriose/metabolismo , Técnicas de Cocultura , Succinatos , Células Estromais/metabolismo
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