Succinic Production Research Articles

Non-alcoholic fatty liver disease in patients with morbid obesity: the gut microbiota axis as a potential pathophysiology mechanism

Background/aimAlterations in gut microbiota are associated with the pathogenesis of metabolic diseases, including metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate gut microbiota composition and functionality in patients with morbid obesity with different degrees of MAFLD, as assessed by biopsy.Subjects/methods110 patients with morbid obesity were evaluated by biopsy obtained during bariatric surgery for MAFLD. Stool samples were collected prior to surgery for microbiota analysis.ResultsGut microbiota from patients with steatosis and non-alcoholic steatohepatitis (NASH) were characterized by an enrichment in Enterobacteriaceae (an ethanol-producing bacteria), Acidaminococcus and Megasphaera and the depletion of Eggerthellaceae and Ruminococcaceae (SCFA-producing bacteria). MAFLD was also associated with enrichment of pathways related to proteinogenic amino acid degradation, succinate production, menaquinol-7 (K2-vitamin) biosynthesis, and saccharolytic and proteolytic fermentation. Basic histological hepatic alterations (steatosis, necroinflammatory activity, or fibrosis) were associated with specific changes in microbiota patterns. Overall, the core microbiome related to basic histological alterations in MAFLD showed an increase in Enterobacteriaceae and a decrease in Ruminococcaceae. Specifically, Escherichia coli was associated with steatosis and necroinflammatory activity, whilst Escherichia-shigella was associated with fibrosis and necroinflammatory activity.ConclusionsWe established a link between gut microbiota alterations and histological injury in liver diagnosis using biopsy. Harmful products such as ethanol or succinate may be involved in the pathogenesis and progression of MAFLD. Thus, these alterations in gut microbiota patterns and their possible metabolic pathways could add information to the classical predictors of MAFLD severity and suggest novel metabolic targets.

Consumption of dietary turmeric promotes fat browning and thermogenesis in association with gut microbiota regulation in high-fat diet-fed mice.

This study was designed to verify the anti-obesity effect of dietary turmeric powder (TP) as a traditional cooking spice and its underlying mechanism. The HFD-fed C57BL/6J mice were supplemented with or without TP (8%) for 12 weeks. The results indicated that the glucolipid metabolism disorder of high-fat diet (HFD)-fed mice was significantly ameliorated through the supplementation of TP. The consumption of TP also induced beige-fat development and brown adipose tissue (BAT)-derived nonshivering thermogenesis in HFD-fed obese mice. 16S rDNA-based microbiota or targeted metabolomics analysis indicated that TP ameliorated the intestinal microbiota dysbiosis and microbial metabolism abnormality caused by HFD, reflected by dramatically increasing the relative abundance of Muribaculaceae, Candidatus_Saccharimonas, and Bifidobacterium and production of short-chain fatty acids (SCFAs) and succinate. Interestingly, TP-induced BAT thermogenesis and iWAT browning were highly correlated with the reconstruction of the gut microbiome and formation of SCFAs and succinate. Collectively, these findings manifest beneficial actions of TP on the promotion of adipose browning and thermogenesis in association with gut microbiota reconstruction, and our findings may provide a promising way for preventing obesity.

A Fermentation State Marker Rule Design Task in Metabolic Engineering.

There are several ways in which mathematical modeling is used in fermentation control, but mechanistic mathematical genome-scale models of metabolism within the cell have not been applied or implemented so far. As part of the metabolic engineering task setting, we propose that metabolite fluxes and/or biomass growth rate be used to search for a fermentation steady state marker rule. During fermentation, the bioreactor control system can automatically detect the desired steady state using a logical marker rule. The marker rule identification can be also integrated with the production growth coupling approach, as presented in this study. A design of strain with marker rule is demonstrated on genome scale metabolic model iML1515 of Escherichia coli MG1655 proposing two gene deletions enabling a measurable marker rule for succinate production using glucose as a substrate. The marker rule example at glucose consumption 10.0 is: IF (specific growth rate μ is above 0.060 h-1, AND CO2 production under 1.0, AND ethanol production above 5.5), THEN succinate production is within the range 8.2-10, where all metabolic fluxes units are mmol ∗ gDW-1 ∗ h-1. An objective function for application in metabolic engineering, including productivity features and rule detecting sensor set characterizing parameters, is proposed. Two-phase approach to implementing marker rules in the cultivation control system is presented to avoid the need for a modeler during production.

Expression of Weimberg xylose utilization pathway for succinate production by cyanobacteria under diurnal condition

BackgroundSuccinate is a widely used platform chemical in plastics and food industries. While autotrophic succinate producing cyanobacteria has previously been demonstrated, a major limitation to its practical utilization is the lack of continuous production at night. MethodsHere we showcase a constant succinate production in diurnal condition by additionally introducing a xylose utilization pathway (XUP) into succinate producing strain. This implemented pathway enables the strain to convert xylose into α-ketoglutarate which then becomes succinate. Significant FindingsThe engineered stain produced succinate with the productivity of 2.4 mg/L/hr under dark condition with xylose supplemented. Additionally, two-fold increase of succinate titer at constant light condition compare to base strain. Together this work showed the installation of xylose utilization system in cyanobacteria is a feasible strategy to provide carbon flux to α-ketoglutarate, which may also be applicable for increasing the production of other TCA cycle derived compounds.

Carbon dioxide and trace oxygen concentrations impact growth and product formation of the gut bacterium Phocaeicola vulgatus

BackgroundThe promising yet barely investigated anaerobic species Phocaeicola vulgatus (formerly Bacteroides vulgatus) plays a vital role for human gut health and effectively produces organic acids. Among them is succinate, a building block for high-value-added chemicals. Cultivating anaerobic bacteria is challenging, and a detailed understanding of P. vulgatus growth and metabolism is required to improve succinate production. One significant aspect is the influence of different gas concentrations. CO2 is required for the growth of P. vulgatus. However, it is a greenhouse gas that should not be wasted. Another highly interesting aspect is the sensitivity of P. vulgatus towards O2. In this work, the effects of varying concentrations of both gases were studied in the in-house developed Respiratory Activity MOnitoring System (RAMOS), which provides online monitoring of CO2, O2, and pressure under gassed conditions. The RAMOS was combined with a gas mixing system to test CO2 and O2 concentrations in a range of 0.25-15.0 vol% and 0.0-2.5 vol%, respectively.ResultsChanging the CO2 concentration in the gas supply revealed a CO2 optimum of 3.0 vol% for total organic acid production and 15.0 vol% for succinate production. It was demonstrated that the organic acid composition changed depending on the CO2 concentration. Furthermore, unrestricted growth of P. vulgatus up to an O2 concentration of 0.7 vol% in the gas supply was proven. The viability decreased rapidly at concentrations larger than or equal to 1.3 vol% O2.ConclusionsThe study showed that P. vulgatus requires little CO2, has a distinct O2 tolerance and is therefore well suited for industrial applications.

From electrons to cancer : Redox shift as a driving force of tumorigenesis

Cancer cells are very diverse but mostly share a common metabolic property: they are strongly glycolytic even though oxygen is available. Herein, the metabolic abnormalities of cancer cells are interpreted as modifications of the electric currents in redox reactions. A lower current in the electron transport chain, an increase of the concentration of reduced cofactors and a partial reversal of the tricarboxylic acid cycle are physical characteristics of several forms of cancer. The existence of electric short-circuits between oxidative branches and reductive branches of the metabolic network argue in favor of an electronic approach of cancer in the nanoscopic scale. These changes of electron flows induce a pseudo-hypoxia and the Warburg effect through succinate production and divert electrons from oxygen to biosynthetic pathways. This new look at cancer may have potential therapeutic applications.

An efficient production of bio-succinate in a novel metabolically engineered Klebsiella oxytoca by rational metabolic engineering and evolutionary adaptation

Klebsiella oxytoca KC004 (ΔadhEΔpta-ackAΔldhAΔbudABΔpflB) was engineered to enhance succinate production. The strain exhibited poor growth without succinate production due to its deficiencies in ATP production and NADH reoxidation. To overcome obstacles, evolutionary adaptation with over 6,000 generations of growth-based selection was conducted. Under anaerobic conditions, enhanced productions of ATP for growth and succinate for NADH reoxidation by the evolved KC004-TF160 strain were coupled to an increased transcript of PEP carboxykinase (pck) while those of genes in the oxidative branch of TCA cycle (gltA, acnAB, and icd), and pyruvate and acetate metabolisms (pykA, acs, poxB and tdcD) were alleviated. The expression of pyruvate dehydrogenase repressor (pdhR) decreased whereas threonine decarboxylase (tdcE) increased. KC004-TF160 produced succinate at 84 g/L (0.84 g/g, 79 % theoretical maximum). KC004-TF160 produced succinate at 0.87 g/g non-pretreated sugarcane molasses without addition of nutrients and buffers. KC004-TF160 may be a microbial platform for commercial production of bio-succinate.

On-line targeted metabolomics for real-time monitoring of relevant compounds in fermentation processes.

Fermentation monitoring is a powerful tool for bioprocess development and optimization. On-line metabolomics is a technology that is starting to gain attention as a bioprocess monitoring tool, allowing the direct measurement of many compounds in the fermentation broth at a very high time resolution. In this work, targeted on-line metabolomics was used to monitor 40 metabolites of interest during three Escherichia coli succinate production fermentation experiments every 5 min with a triple quadrupole mass spectrometer. This allowed capturing high-time resolution biological data that can provide critical information for process optimization. For nine of these metabolites, simple univariate regression models were used to model compound concentration from their on-line mass spectrometry peak area. These on-line metabolomics univariate models performed comparably to vibrational spectroscopy multivariate partial least squares regressions models reported in the literature, which typically are much more complex and time consuming to build. In conclusion, this work shows how on-line metabolomics can be used to directly monitor many bioprocess compounds of interest and obtain rich biological and bioprocess data.

Designing a periplasmic photosynthetic biohybrid system for succinate and electric energy production

The emergence of photosynthetic biohybrid systems provides an environmentally friendly and sustainable approach to produce fuels and chemicals in microbial cell factories. However, the low efficiency of electron transfer between semiconductors and microorganisms hinders production efficiency. In this study, a periplasmic photosynthetic biohybrid system (PPB) was developed in E. coli through biological self-synthesis and optimized through engineering the periplasmic cytochrome network and cell membrane fluidity. The PPB significantly increased succinate production to a titer of 121.8 g/L in a 5 L fermenter by improving the reducing equivalents utilization. Additionally, the PPB was employed to establish a glucose-utilizing microbial consortium that exhibited robust performance, producing consistent electric energy output for a minimum of 17 days and achieving a maximum power density of 225.3 mW/m2. These findings demonstrate the capability of the PPB to enhance chemical production and generate electric energy from renewable carbon sources, thereby driving advances in green chemistry and promoting environmentally friendly industrial processes.

A novel SUCNR1 inhibitor alleviates dysbiosis through inhibition of host responses without direct interaction with host microbiota.

Type 2 diabetes (T2D) is a chronic metabolic disorder in which insulin resistance and impaired insulin secretion result in altered metabolite balance, specifically elevated levels of circulating glucose and succinate, which increases the risk of many pathologies, including periodontitis. Succinate, a tricarboxylic acid (TCA) cycle intermediate, can be produced and metabolized by both host cells and host microbiota, where elevated levels serve as an inflammation and pathogen threat signal through activating the succinate G protein-coupled receptor, SUCNR1. Modulating succinate-induced SUCNR1 signaling remains a promising therapeutic approach for pathologies resulting in elevated levels of succinate, such as T2D and periodontitis. Here, we demonstrate hyperglycemia and elevated intracellular succinate in a T2D mouse model and determine gut microbiome composition. Drawing on previous work demonstrating the ability of a novel SUCNR1 antagonist, compound 7a, to block inflammation and alleviate dysbiosis in a mouse model, we examined if compound 7a has an impact on the growth and virulence gene expression of bacterial and fungal human microbiota in vitro, and if 7a could reduce bone loss in a periodontitis-induced mouse model. T2D mice harbored a significantly different gut microbiome, suggesting the altered metabolite profile of T2D causes shifts in host-microbial community structure, with enrichment in succinate producers and consumers and mucin-degrading bacteria. Bacterial and fungal cultures showed that 7a did not influence growth or virulence gene expression, suggesting the therapeutic effects of 7a are a direct result of 7a interacting with host cells and that alterations in microbial community structure are driven by reduced host SUCNR1 signaling. This work further suggests that targeting SUCNR1 signaling is a promising therapeutic approach in metabolic, inflammatory, or immune disorders with elevated succinate levels.

Effect of inoculating Pichia spp. starters on flavor formation of fermented chili pepper: Metabolomics and genomics approaches

The influence of Pichia spp. on flavor formation and metabolic pathways during chili pepper fermentation was investigated in this study. Multiple omics approaches were employed, including metabolomics analysis to identify volatile and non-volatile flavor compounds, and genomic analysis to gain insights into the underlying molecular mechanism driving flavor formation of chili peppers inoculated with Pichia spp. The results showed that inoculation with Pichia spp. accelerated fermentation process of chili peppers compared to spontaneous fermentation. Metabolomics analysis showed P. fermentans promoted characteristic terpenes [e.g., (Z)-β-ocimene and linalool], L-glutamate, gamma-aminobutyric acid, and succinate production, while P. manshurica produced more alcohols (e.g., isoamyl alcohol and phenylethyl alcohol) and phenols (e.g., 4-ethylguaiacol and 2-methoxy-4-methylphenol). Genomics analysis revealed that a substantial portion of the genes in Pichia spp. were associated with amino acid and carbohydrate metabolism. Specifically, the pathways involved in amino acid metabolism and the release of glycoside-bound aromatic compounds were identified as the primary drivers behind the unique flavor of fermented chili peppers, facilitated by Pichia spp.

Oligofructose alone and in combination with 2'fucosyllactose induces physiologically relevant changes in γ-aminobutyric acid and organic acid production compared to sole 2'fucosyllactose supplementation: an in vitro study.

We explored the potential for the prebiotic oligofructose and prebiotic candidate 2'fucosyllactose, alone and in combination (50:50 blend) to induce physiologically relevant increases in neurotransmitter (γ-aminobutyric acid, serotonin, tryptophan, and dopamine) and organic acid (acetate, propionate, butyrate, lactate, and succinate) production as well as microbiome changes using anaerobic pH-controlled in vitro batch culture fermentations over 48h. Changes in organic acid and neurotransmitter production were assessed by gas chromatography and liquid chromatography and, bacterial enumeration using fluorescence in situ hybridization, respectively. Both oligofructose and oligofructose/2'fucosyllactose combination fermentations induced physiologically relevant concentrations of γ-aminobutyric acid, acetate, propionate, butyrate, and succinate at completion (all P ≤ .05). A high degree of heterogeneity was seen amongst donors in both neurotransmitter and organic acid production in sole 2'FL fermentations suggesting a large responder/nonresponder status exists. Large increases in Bifidobacterium, Lactobacillus, and Bacteroides numbers were detected in oligofructose fermentation, smallest increases being detected in 2'fucosyllactose fermentation. Bacterial numbers in the combined oligofructose/2'fucosyllactose fermentation were closer to that of sole oligofructose. Our results indicate that oligofructose and oligofructose/2'fucosyllactose in combination have the potential to induce physiologically relevant increases in γ-aminobutyric and organic acid production along with offsetting the heterogenicity seen in response to sole 2'fucosyllactose supplementation.

Streamlined identification of strain engineering targets for bioprocess improvement using metabolic pathway enrichment analysis

Metabolomics is a powerful tool for the identification of genetic targets for bioprocess optimisation. However, in most cases, only the biosynthetic pathway directed to product formation is analysed, limiting the identification of these targets. Some studies have used untargeted metabolomics, allowing a more unbiased approach, but data interpretation using multivariate analysis is usually not straightforward and requires time and effort. Here we show, for the first time, the application of metabolic pathway enrichment analysis using untargeted and targeted metabolomics data to identify genetic targets for bioprocess improvement in a more streamlined way. The analysis of an Escherichia coli succinate production bioprocess with this methodology revealed three significantly modulated pathways during the product formation phase: the pentose phosphate pathway, pantothenate and CoA biosynthesis and ascorbate and aldarate metabolism. From these, the two former pathways are consistent with previous efforts to improve succinate production in Escherichia coli. Furthermore, to the best of our knowledge, ascorbate and aldarate metabolism is a newly identified target that has so far never been explored for improving succinate production in this microorganism. This methodology therefore represents a powerful tool for the streamlined identification of strain engineering targets that can accelerate bioprocess optimisation.

Pursuing single or combined wheat straw based poly(butylene succinate) production routes: A life cycle approach of first- and second-generation feedstocks

The depletion of fossil resources and the climate change crisis call for an urgent shift to production pathways based on renewable and low-carbon sources. In addition, plastic pollution worldwide motivates the identification of new sources for their bio-based counterparts, which have an increasing demand. This research aims to evaluate the environmental feasibility of different cereal-based feedstocks for the production of poly(butylene succinate) (PBS), which is obtained from the polymerisation of succinic acid (SA) and 1,4 butanediol (BDO) monomers. The baseline scenario analysed corresponds to the use of wheat straw as a source of the fermentable sugars. Furthermore, five other cereal-based production routes combining first-generation (1G) feedstocks such as wheat and maize grain, and second-generation (2G) feedstocks, such as sorghum, barley straw, and maize stover, combined with wheat straw, were evaluated. The Life Cycle Assessment (LCA) methodology was used to identify the main hotspots of these valorisation routes at the early stage of the biorefinery design, considering all the burden categories provided by the ReCiPe impact method. The results showed that the straw-based PBS profile reached a Global Warming Potential of 3.43 kg CO2eq, whereas a range value from 2.34 to 7.27 kg CO2eq was estimated when wheat straw is combined with sorghum and barley straw, respectively. The pre-treatment stage represents a substantial impact on the strategy considered to produce fermentable sugars, particularly, for barley straw. Therefore, improvements are still required to reduce the energy demand and increase the sugar yield.

Dynamic Domain Links Substrate Binding and Catalysis in the Factor-Inhibiting-HIF-1.

The interplay between active-site chemistry and functionally relevant enzyme motions can provide useful insights into selective enzyme modulation. Modulation of the hypoxia-sensing function of factor-inhibiting-HIF-1 (FIH) enzyme is a potential therapeutic strategy in disease states such as ischemia and cancer. The hypoxia-sensing function of FIH relies in major part on the tight coupling of the first half of the catalytic mechanism which involves O2 activation and eventual succinate production to the second half which involves HIF-1α/CTAD substrate hydroxylation. In this study, we demonstrate the role of a loop hinge domain in FIH (FIH102-118) called the 100s loop in maintaining this particular tight coupling. Molecular dynamics patterns from Gaussian Network Model (iGNM) database analysis of FIH identified the 100s loop as one dynamic domain containing a hinge residue (Tyr102) with a potential substrate positioning role. Enzymological and biophysical studies of the 100s loop point mutants revealed altered enzyme kinetics with the exception of the conservative FIH mutant Y102F, which suggests a sterics-related role for this residue. Removal of the bulk of Tyr102 (Y102A) resulted in succinate production, autohydroxylation, and an O2 binding environment comparable to wild-type FIH. However, the HIF-1α/CTAD substrate hydroxylation of this mutant was significantly reduced which implies that (1) the FIH loop hinge residue Tyr102 does not affect O2 activation, (2) the stacking steric interaction of Tyr102 is important in substrate positioning for productive hydroxylation, and (3) Tyr102 is important for the synchronization of O2 activation and substrate hydroxylation.

Fluctuating pH for efficient photomixotrophic succinate production

Cyanobacteria are attracting increasing attention as a photosynthetic chassis organism for diverse biochemical production, however, photoautotrophic production remains inefficient. Photomixotrophy, a method where sugar is used to supplement baseline autotrophic metabolism in photosynthetic hosts, is becoming increasingly popular for enhancing sustainable bioproduction with multiple input energy streams. In this study, the commercially relevant diacid, succinate, was produced photomixotrophically. Succinate is an important industrial chemical that can be used for the production of a wide array of products, from pharmaceuticals to biopolymers. In this system, the substrate, glucose, is transported by a proton symporter and the product, succinate, is hypothesized to be transported by another proton symporter, but in the opposite direction. Thus, low pH is required for the import of glucose and high pH is required for the export of succinate. Succinate production was initiated in a pH 7 medium containing bicarbonate. Glucose was efficiently imported at around neutral pH. Utilization of bicarbonate by CO2 fixation raised the pH of the medium. As succinate, a diacid, was produced, the pH of the medium dropped. By repeating this cycle with additional pH adjustment, those contradictory requirements for transport were overcome. pH affects a variety of biological factors and by cycling from high pH to neutral pH processes such as CO2 fixation rates and CO2 solubility can vary. In this study the engineered strains produced succinate during fluctuating pH conditions, achieving a titer of 5.0 g L−1 after 10 days under shake flask conditions. These results demonstrate the potential for photomixotrophic production as a viable option for the large-scale production of succinate.

Refined fiber inulin promotes inflammation-associated colon tumorigenesis by modulating microbial succinate production.

There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the effects of refined DFs on intestinal health remain unclear. Therefore, we elucidated the impact of the refined DF inulin on colonic inflammation and tumorigenesis. Four-week-old wild-type (WT) mice were fed diets containing insoluble DF cellulose (control) or refined DF inulin for 4 weeks. A subgroup of mice was then switched to drinking water containing dextran sulfate sodium (DSS, 1.4% wt/vol) for colitis induction. In another subgroup of mice, colitis-associated colorectal cancer (CRC) was initiated with three 7-day alternate cycles of DSS following an initial dose of mutagenic substance azoxymethane (AOM; 7.5 mg/kg body weight; i.p.). Post 7 weeks of AOM treatment, mice were euthanized and examined for CRC development. Mice consuming inulin-containing diet exhibited severe colitis upon DSS administration, as evidenced by more body weight loss, rectal bleeding, and increased colonic inflammation than the DSS-treated control group. Correspondingly, histological analysis revealed extensive disruption of colon architecture and massive infiltration of immune cells in the inulin-fed group. We next examined the effect of inulin on CRC development. Surprisingly, significant mortality (~50%) was observed in the inulin-fed but not in the control group during the DSS cycle. Consequently, the remaining inulin-fed mice, which completed the study exhibited extensive colon tumorigenesis. Immunohistochemical characterization showed comparatively high expression of the cell proliferation marker Ki67 and activation of the Wnt signaling in tumor sections obtained from the inulin-fed group. Gut microbiota and metabolite analysis revealed expansion of succinate producers and elevated cecal succinate in inulin-fed mice. Human colorectal carcinoma cells (HCT116) proliferated more rapidly when supplemented with succinate in an inflamed environment, suggesting that elevated luminal succinate may contribute to tumorigenesis. Our study uncovers that supplementation of diet with refined inulin induces abnormal succinate accumulation in the intestinal lumen, which in part contributes to promoting colon inflammation and tumorigenesis.

Citrate Synthase Overexpression of Pseudomonas putida Increases Succinate Production from Acetate in Microaerobic Cultivation.

Acetate is an end-product of anaerobic biodegradation and one of the major metabolites of microbial fermentation and lingo-cellulosic hydrolysate. Recently, acetate has been highlighted as a feedstock to produce value-added chemicals. This study examined acetate conversion to succinate by citrate synthase (gltA)-overexpressed Pseudomonas putida under microaerobic conditions. The acetate metabolism is initiated with the gltA enzyme, which converts acetyl-CoA to citrate. gltA-overexpressing P. putida (gltA-KT) showed an ∼50% improvement in succinate production compared to the wild type. Under the optimal pH of 7.5, the accumulation of succinate (4.73 ± 0.6 mM in 36 h) was ∼400% higher than that of the wild type. Overall, gltA overexpression alone resulted in 9.5% of the maximum theoretical yield in a minimal medium with acetate as the sole carbon source. This result shows that citrate synthase is important in acetate conversion to succinate by P. putida under microaerobic conditions.

Bioproduction of succinic acid from potato waste. Kinetic modeling

Succinic acid is a key chemical platform for the implementation of biorefineries and, therefore, for the development of a sustainable bioeconomy. In this work, succinic acid anaerobic production by Actinobacillus succinogenes from potato waste and glucose was carried out. Firstly, a simple kinetic model was developed to accurately predict the evolution of succinic acid, substrate, by-products, and biomass based on bottle experiments performed at different initial glucose concentrations. Secondly, experiments with an acid hydrolysate of potato waste as carbon source were performed in orbitally shaken bottles and bioreactor to compare the fermentation performance of the potato waste with the pure glucose. Using this hydrolysate, 32.2 g‧L-1 of succinic acid were obtained with a productivity of 0.64 g‧L-1‧h-1, improving SA yield by 37% compared to results with pure glucose. This is one of the highest values to date for succinic acid bioproduction from food residues (0.92 g‧g-1). Finally, the proposed kinetic model was successfully applied to the fermentation data obtained from potato waste fermentation, being this type of models a highly valuable tool for future techno-economic analysis of the bioprocess.

Microglial Metabolic Reprogramming: Emerging Insights and Therapeutic Strategies in Neurodegenerative Diseases.

Microglia, the resident immune cells of the central nervous system, play a critical role in maintaining brain homeostasis. However, in neurodegenerative conditions, microglial cells undergo metabolic reprogramming in response to pathological stimuli, including Aβ plaques, Tau tangles, and α-synuclein aggregates. This metabolic shift is characterized by a transition from oxidative phosphorylation (OXPHOS) to glycolysis, increased glucose uptake, enhanced production of lactate, lipids, and succinate, and upregulation of glycolytic enzymes. These metabolic adaptations result in altered microglial functions, such as amplified inflammatory responses and diminished phagocytic capacity, which exacerbate neurodegeneration. This review highlights recent advances in understanding the molecular mechanisms underlying microglial metabolic reprogramming in neurodegenerative diseases and discusses potential therapeutic strategies targeting microglial metabolism to mitigate neuroinflammation and promote brain health. Microglial Metabolic Reprogramming in Neurodegenerative Diseases This graphical abstract illustrates the metabolic shift in microglial cells in response to pathological stimuli and highlights potential therapeutic strategies targeting microglial metabolism for improved brain health.