Shifts In Metabolic Pathways Research Articles

CRISPR/Cas9 mediated CHS2 mutation provides a new insight into resveratrol biosynthesis by causing a metabolic pathway shift from flavonoids to stilbenoids in Vitis davidii cells

Abstract Resveratrol is an important phytoalexin that adapts to and responds to stressful conditions, plays various roles in health and medical therapies. However, it is only found in a limited number of plant species in low concentrations, which hinders its development and utilization. Chalcone synthase (CHS) and stilbene synthase (STS) catalyze the same substrates to produce flavonoids and resveratrol, respectively. However, it remains unclear how CHS and STS compete in metabolite synthesis. In this study, two CHS2 mutant cell lines (MT1 and MT2) were generated using CRISPR/Cas9 genome editing. These CHS2 mutant cell lines exhibited abundant mutations in CHS2, leading to the premature termination of protein translation and subsequent CHS2 knockout. Amplicon sequencing confirmed comprehensive CHS2 knockout in MT1, whereas the wild-type sequence remained predominant in the MT2 cell line. Transcriptome and RT-qPCR results showed a significant downregulation of genes involved in flavonoid biosynthesis, including CHS2, CHS3, F3H, F3’H, DFR, FLS, LDOX, among others, resulting in decreased flavonoid accumulation, such as anthocyanins, proanthocyanidins, quercetin, and kaempferol. Conversely, STS genes involved in stilbenoid biosynthesis were upregulated competing with the flavonoid pathway. Consequently, there was a marked increase in stilbenoids, including resveratrol, piceatannol, piceid and pterostilbene, with a 4.1-fold increase in resveratrol and a 5.3-fold increase in piceid (a derivative of resveratrol) observed in CHS2 mutant cell lines. This research demonstrates that CHS2 mutation induces a shift from flavonoid biosynthesis towards stilbenoid biosynthesis, offering new insights into metabolite biosynthesis and regulation, as well as an alternative solution for natural resveratrol production, and a novel breeding approach for eliminating non-target agronomic traits using CRISPR-Cas9.

Succession from acetoclastic to hydrogenotrophic microbial community during sewage sludge anaerobic digestion for bioenergy production.

To assess microbial dynamics during anaerobic digestion (AD) of sewage sludge (SWS) from a municipal Wastewater Treatment Plant (WWTP), a Biochemical Methane Potential (BMP) assay at 37°C under mono-digestion conditions was conducted. Utilizing the Illumina MiSeq platform, 16S ribosomal RNA (rRNA) gene sequencing unveiled a core bacterial community in the solid material, showcasing notable variations in profiles. The research investigates changes in microbial communities and metabolic pathways to understand their impact on the efficiency of the digestion process. Prior to AD, the relative abundance in SWS was as follows: Proteobacteria > Bacteroidota > Actinobacteriota. Post-AD, the relative abundance shifted to Firmicutes > Synergistota > Proteobacteria, with Sporanaerobacter and Clostridium emerging as dominant genera. Notably, the methanogenic community underwent a metabolic pathway shift from acetoclastic to hydrogenotrophic in the lab-scale reactors. At the genus level, Methanosaeta, Methanolinea, and Methanofastidiosum predominated initially, while post-AD, Methanobacterium, Methanosaeta, and Methanospirillum took precedence. This metabolic transition may be linked to the increased abundance of Firmicutes, particularly Clostridia, which harbor acetate-oxidizing bacteria facilitating the conversion of acetate to hydrogen.

Metabolic Shift in Porcine Spermatozoa during Sperm Capacitation-Induced Zinc Flux.

Mammalian spermatozoa rely on glycolysis and mitochondrial oxidative phosphorylation for energy leading up to fertilization. Sperm capacitation involves a series of well-regulated biochemical steps that are necessary to give spermatozoa the ability to fertilize the oocyte. Additionally, zinc ion (Zn2+) fluxes have recently been shown to occur during mammalian sperm capacitation. Semen from seven commercial boars was collected and analyzed using image-based flow cytometry before, after, and with the inclusion of 2 mM Zn2+ containing in vitro capacitation (IVC) media. Metabolites were extracted and analyzed via Gas Chromatography-Mass Spectrometry (GC-MS), identifying 175 metabolites, with 79 differentially abundant across treatments (p < 0.05). Non-capacitated samples showed high levels of respiration-associated metabolites including glucose, fructose, citric acid, and pyruvic acid. After 4 h IVC, these metabolites significantly decreased, while phosphate, lactic acid, and glucitol increased (p < 0.05). With zinc inclusion, we observed an increase in metabolites such as lactic acid, glucitol, glucose, fructose, myo-inositol, citric acid, and succinic acid, while saturated fatty acids including palmitic, dodecanoic, and myristic acid decreased compared to 4 h IVC, indicating regulatory shifts in metabolic pathways and fatty acid composition during capacitation. These findings underscore the importance of metabolic changes in improving artificial insemination and fertility treatments in livestock and humans.

The shift of carbon metabolic pathways mediated by key rhizosphere microbes of exotic plants affects organic carbon

The shift of carbon metabolic pathways mediated by key rhizosphere microbes of exotic plants affects organic carbon

Serum lipidomic profiling of dairy calves fed milk replacers containing animal or vegetable fats

Vegetable fat blends are commonly used as fat sources in milk replacers (MR) for calves, but their composition differs considerably from that of bovine milk fat. The aim of this study was to investigate the serum lipid profile of pre-weaned calves fed twice-daily MR containing 30% fat (% DM). Upon arrival, 30 male Holstein-Friesian calves (BW = 45.6 ± 4.0 kg, age = 2.29 ± 0.8 d) were randomly assigned to 2 experimental diets (n = 15 per treatment): one MR was derived from either vegetable fats (VG; 80% rapeseed and 20% coconut fats) or animal fats (AN; 65% Packer's lard and 35% dairy cream). The 2 MR formulas contained 30% fat, 24% CP, and 36% lactose. Calves were housed indoors in individual pens with ad libitum access to chopped straw and water. Daily milk allowances were 6.0 L from d 1 to 5, 7.0 L from d 6 to 9, and 8.0 L from d 10 to 35, divided into 2 equal meals and prepared at 13.5% solids. An untargeted liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) method was employed to analyze the lipid profiles in the serum of calves sampled from the jugular vein at 35 d of age. In total, 594 lipids were characterized, comprising 25 different lipid classes. Principal component analysis (PCA) showed significant separation between VG and AN, indicating different lipid profiles in the serum. An orthogonal partial least squares discriminant analysis (OPLS-DA) classification model was used to further validate the distinction between the 2 treatment groups. The model exhibited a robust class separation and high predictive accuracy. Using a Volcano plot (fold change threshold ≥1.5 and false discovery rate ≤0.05), it was observed that calves fed AN had higher levels of 39 lipid species in serum than calves fed VG, whereas 171 lipid species were lower in the AN group. Lipid classes, such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), triglycerides (TG), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE), were different. In particular, PC and PE were observed at lower levels in calves fed AN, possibly indicating shifts in cell membrane characteristics, intracellular signaling, and liver functions. In addition, a decrease in certain triglyceride (TG) species was observed in calves fed AN, including a decrease in TG species such as TG 36:0 and TG 38:0, possibly related to variations in the content of certain fatty acids (FA) within the AN MR, such as C10:0, C12:0, C14:0, and C18:0 compared with the VG MR. Calves fed AN had lower levels of LPC and LPE, and lyso-phosphatidylinositol (LPI), SM, and phosphatidylinositol (PI) species than calves fed VG, suggesting shifts in lipoprotein and lipid metabolic pathways. In conclusion, these results deepen the understanding of how lipid sources in MR can modulate the serum lipidome profiles of dairy calves.

Pan-Cancer, Genome-Scale Metabolic Network Analysis of over 10,000 Patients Elucidates Relationship between Metabolism and Survival.

Despite the high variability in cancer biology, cancers nevertheless exhibit cohesive hallmarks across multiple cancer types, notably dysregulated metabolism. Metabolism plays a central role in cancer biology, and shifts in metabolic pathways have been linked to tumor aggressiveness and likelihood of response to therapy. We therefore sought to interrogate metabolism across cancer types and understand how intrinsic modes of metabolism vary within and across indications and how they relate to patient prognosis. We used context specific genome-scale metabolic modeling to simulate metabolism across 10,915 patients from 34 cancer types from The Cancer Genome Atlas and the MMRF-COMMPASS study. We found that cancer metabolism clustered into modes characterized by differential glycolysis, oxidative phosphorylation, and growth rate. We also found that the simulated activities of metabolic pathways are intrinsically prognostic across cancer types, especially tumor growth rate, fatty acid biosynthesis, folate metabolism, oxidative phosphorylation, steroid metabolism, and glutathione metabolism. This work shows the prognostic power of individual patient metabolic modeling across multiple cancer types. Additionally, it shows that analyzing large-scale models of cancer metabolism with survival information provides unique insights into underlying relationships across cancer types and suggests how therapies designed for one cancer type may be repurposed for use in others.

Targeted Quantification of Glutathione/Arginine Redox Metabolism Based on a Novel Paired Mass Spectrometry Probe Approach for the Functional Assessment of Redox Status.

Glutathione (GSH) redox control and arginine metabolism are critical in regulating the physiological response to injury and oxidative stress. Quantification assessment of the GSH/arginine redox metabolism supports monitoring metabolic pathway shifts during pathological processes and their linkages to redox regulation. However, assessing the redox status of organisms with complex matrices is challenging, and single redox molecule analysis may not be accurate for interrogating the redox status in cells and in vivo. Herein, guided by a paired derivatization strategy, we present a new ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based approach for the functional assessment of biological redox status. Two structurally analogous probes, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and newly synthesized 2-methyl-6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (MeAQC), were set for paired derivatization. The developed approach was successfully applied to LPS-stimulated RAW 264.7 cells and HDM-induced asthma mice to obtain quantitative information on GSH/arginine redox metabolism. The results suggest that the redox status was remarkably altered upon LPS and HDM stimulation. We expect that this approach will be of good use in a clinical biomarker assay and potential drug screening associated with redox metabolism, oxidative damage, and redox signaling.

Ultrasonication-induced metabolic pathway shifts and reduced electron carrier washout with biomass enhanced hydrogen yield in a continuous stirred tank reactor

Biohydrogen is pivotal for hydrogen economy, providing a renewable, carbon–neutral source of hydrogen from organic waste and biomass. It addresses environmental concerns and supports circular economy principles. However, challenges like managing metabolic pathways and dissolved hydrogen hinder attainment of higher hydrogen yields. This study explored the impact of organic loading rates (OLR) and ultrasonication on glucose fermentation by Clostridium pasteurianum for biohydrogen production.Results showed ultrasonication, particularly at 10 g/L.d OLR, increased hydrogen yield from 1.04 to 1.28 mol-H₂/mol-glucose. Higher OLR boosted biogas production, and at 10 g/L.d OLR, ultrasonication improved hydrogen purity from 46% to 53%, enhancing yield by 13%. C. pasteurianum shifted metabolic pathways under higher OLR, increasing lactate production to address redox imbalance. However, ultrasonication negatively affected lactate and acetate reutilisation, redirecting carbon flux from lactate to butyrate, increasing hydrogen yield.Combining ultrasonication and increased OLR enhanced glycolysis carbon flux by 14.5% and reduced biomass carbon flux by 10.5%. Hydrogen yield, influenced by glycolysis carbon flux, reached 82% under ultrasonication and increased OLR. Ultrasonication mitigated inhibitory effects on electron carrier molecule re-oxidation, emphasising the need to balance biomass, dissolved hydrogen concentration, and OLR for optimal hydrogen recovery.Despite decreased acetate/butyrate ratio and unchanged theoretical hydrogen production with ultrasonication, hydrogen yield increased. This likely resulted from reduced electron carrier molecule wastage with biomass, influenced by higher biomass concentration and ultrasonication. The study underscored preventing electron carrier molecule washout for higher hydrogen production and recommends using batch reactors over continuous stirred tank reactors in dark fermentation operations.

Myeloid cell-associated aromatic amino acid metabolism facilitates CNS myelin regeneration

Regulation of myeloid cell activity is critical for successful myelin regeneration (remyelination) in demyelinating diseases, such as multiple sclerosis (MS). Here, we show aromatic alpha-keto acids (AKAs) generated from the amino acid oxidase, interleukin-4 induced 1 (IL4I1), promote efficient remyelination in mouse models of MS. During remyelination, myeloid cells upregulated the expression of IL4I1. Conditionally knocking out IL4I1 in myeloid cells impaired remyelination efficiency. Mice lacking IL4I1 expression exhibited a reduction in the AKAs, phenylpyruvate, indole-3-pyruvate, and 4-hydroxyphenylpyruvate, in remyelinating lesions. Decreased AKA levels were also observed in people with MS, particularly in the progressive phase when remyelination is impaired. Oral administration of AKAs modulated myeloid cell-associated inflammation, promoted oligodendrocyte maturation, and enhanced remyelination in mice with focal demyelinated lesions. Transcriptomic analysis revealed AKA treatment induced a shift in metabolic pathways in myeloid cells and upregulated aryl hydrocarbon receptor activity in lesions. Our results suggest myeloid cell-associated aromatic amino acid metabolism via IL4I1 produces AKAs in demyelinated lesions to enable efficient remyelination. Increasing AKA levels or targeting related pathways may serve as a strategy to facilitate the regeneration of myelin in inflammatory demyelinating conditions.

Effect of pH on metabolic pathway shift in fermentation and electro-fermentation of xylose by Clostridium autoethanogenum

Clostridium autoethanogenum can to convert waste gases (CO2, CO, H2) and xylose from hydrolyzed biomass into acetate, lactate, formate, ethanol and 2,3-butanediol, being a candidate for the transformation of waste streams of lignocellulosic biorefineries. Electro-fermentation (EF) modify the pattern of traditional fermentations resulting in improved product yields as has been shown when using Clostridium strains. The aim of this work was to evaluate the influence of pH on microbial growth and product distribution during fermentation and EF of xylose by C. autoethanogenum DSM10061. Fermentation and EF were carried out in a H-type reactor at three controlled pH: 5.0, 5.5 and 5.8, and at a fixed potential of −600 mV (versus Ag/AgCl) in the EF. The experiments showed that maximum biomass concentration increased as the pH increased in fermentation and EF. In accordance with maximum biomass reached, the highest substrate conversion was observed at pH 5.8 for both systems, with 76.80 % in fermentation and 96.18 % in EF. Moreover, the highest concentrations of acetic acid (1.41 ± 0.07 g L−1) and ethanol (1.45 ± 0.15 g L−1) were obtained at the end of cultures in the EF at pH 5.8. The production of lactic and formic acid decreased by the application of the external potential regardless of the pH value, reaching the lowest productivity at pH 5.8. In contrast, the specific productivity of acetic acid and ethanol was lower in both fermentation and EF at the lowest pH. Furthermore, the presence of 0.06 g L−1 of 2,3-butanediol was only detected in EF at pH 5.8. The results revealed that EF modulated microbial metabolism, which can be explained by a possible increased generation of NADP+/NADPH cofactors, which would redirect the metabolic pathway to more reduced products.

Gestational GenX and PFOA exposures induce hepatotoxicity, metabolic pathway, and microbiome shifts in weanling mice

Ammonium perfluoro (2-methyl-3-oxahexanoate) (GenX), a replacement for perfluorooctanoic acid (PFOA), has been detected in multiple environmental media and biological samples worldwide. Accumulated evidence implies that GenX exposure might exert adverse health effects, although the underlying mechanisms have not been fully revealed. In this study, pregnant BALB/c mice were exposed to GenX (2 mg/kg/day), PFOA (1 mg/kg/day), or Milli-Q water by gavage from the first day of gestation (GD0) until GD21. Necropsy and tissue collection were conducted in pups at 4 weeks of age. PFOA and GenX induced similar histopathological changes in both the liver and the intestinal mucosa, accompanied by higher serum levels of alanine and aspartate aminotransferase. Moreover, the capacity of hepatic glycogen storage and intestinal mucus secretion were significantly decreased, suggesting dysfunction of liver metabolism and the intestinal mucosal barrier. A total of 637 and 352 differentially expressed genes (DEGs) were identified in the liver tissues of GenX and PFOA group, respectively. Most of the enriched pathways from the DEGs by KEGG enrichment analysis were metabolism-associated. Moreover, overexpression of CYP4A14, Sult2a1, Cpt1b, Acaa1b, Igfbp1, Irs-2 and decreased expression of Gys2 were observed in livers of GenX exposed pups, supporting the hypothesis that there was metabolic disruption. Furthermore, DNA damage and cell cycle arrest proteins (Gadd45β, p21, Ppard) were significantly increased, while cell proliferation-related proteins (Cyclin E, Myc, EGFR) were decreased by gestational GenX exposure in the pups' liver. In addition, imbalance of gut microbiota and dysfunction of the intestinal mucosa barrier might contribute to hepatotoxicity at least in part. Taken together, our results suggested that gestational GenX exposure triggered metabolic disorder, which might be responsible for the hepatotoxicity in the pups in addition to dysfunction of the intestinal mucosa barrier. This study enriches the mechanisms of GenX-induced developmental hepatotoxicity by associating metabolic disorder with intestinal homeostasis.

Unknown bacterial species lead to soil CO2 emission reduction by promoting lactic fermentation in alpine meadow on the Qinghai-Tibetan Plateau

Highly variable soil microbial respiration among grasslands has been identified as a major cause of uncertainty in regional carbon (C) budget estimation in the Qinghai-Tibetan Plateau; microbial metabolism mechanisms might explain this variation, but remain elusive. Therefore, we investigated soil CO2 production in incubated soils and detected the associated functional genes at four sampling sites from two major alpine grasslands on the Qinghai-Tibetan Plateau. The results showed that the cumulative CO2 emissions from alpine meadow soils were 71 %–83 % lower than those from alpine steppe soils. Both the enriched genes abundance encoding fermentation and glycolysis (Embden-Meyerhof pathway (EMP)) and the diminished genes encoding tricarboxylic acid cycle (TCA) and phosphate pentose pathway (PPP) explained the CO2 emission reduction in the alpine meadow soils. The EMP: PPP and fermentation: TCA cycle ratios in alpine meadow soils were 1.45- and 1.50-fold higher than those in alpine steppe soils, respectively. Such shifts in metabolic pathways were primarily caused by the increasing dominance of an unknown species of Desulfobacteraceae with high glycolytic potential, carrying a higher abundance of ldh genes during fermentation. These unknown species were promoted by warmer temperatures and higher precipitation in the alpine meadows. Further studies on the unknown species would enhance our understanding and predictability of C cycling in alpine grasslands.

Cardiac Metabolism, Reprogramming, and Diseases.

Cardiovascular diseases (CVD) account for the largest bulk of deaths worldwide, posing a massive burden on societies and the global healthcare system. Besides, the incidence and prevalence of these diseases are on the rise, demanding imminent action to revert this trend. Cardiovascular pathogenesis harbors a variety of molecular and cellular mechanisms among which dysregulated metabolism is of significant importance and may even proceed other mechanisms. The healthy heart metabolism primarily relies on fatty acids for the ultimate production of energy through oxidative phosphorylation in mitochondria. Other metabolites such as glucose, amino acids, and ketone bodies come next. Under pathological conditions, there is a shift in metabolic pathways and the preference of metabolites, termed metabolic remodeling or reprogramming. In this review, we aim to summarize cardiovascular metabolism and remodeling in different subsets of CVD to come up with a new paradigm for understanding and treatment of these diseases.

Arabidopsis T-DNA mutants affected in TRDMT1/DNMT2 show differential protein synthesis and compromised stress tolerance.

TRDMT1/DNMT2 belongs to the conserved family of nucleic acid methyltransferases. Unlike the animal systems, studies on TRDMT1/DNMT2 in land plants have been limited. We show that TRDMT1/DNMT2 is strongly conserved in the green lineage. Studies in mosses have previously shown that TRDMT1/DNMT2 plays a crucial role in modulating molecular networks involved in stress perception and signalling and in transcription/stability of specific tRNAs under stress. To gain deeper insight into its biological roles in a flowering plant, we examined more closely the previously reported Arabidopsis SALK_136635C line deficient in TRDMT1/DNMT2 function [Goll MG etal. (2006) Science 311, 395-398]. RNAs derived from Arabidopsis Dnmt2-deficient plants lacked m5 C38 in tRNAAsp . In this study, by transient expression assays we show that Arabidopsis TRDMT1/DNMT2 is distributed in the nucleus, cytoplasm and RNA-processing bodies, suggesting a role for TRDMT1/DNMT2 in RNA metabolic processes possibly by shuttling between cellular compartments. Bright-field and high-resolution SEM and qPCR analysis reveal roles of TRDMT1/DNMT2 in proper growth and developmental progression. Quantitative proteome analysis by LC-MS/MS coupled with qPCR shows AtTRDMT1/AtDNMT2 function to be crucial for protein synthesis and cellular homeostasis via housekeeping roles and proteins with poly-Asp stretches and RNA pol II activity on selected genes are affected in attrdmt1/atdnmt2. This shift in metabolic pathways primes the mutant plants to become increasingly sensitive to oxidative and osmotic stress. Taken together, our study sheds light on the mechanistic role of TRDMT1/DNMT2 in a flowering plant.

A state-of-the-art on the application of nanotechnology for enhanced biohydrogen production

Carbon footprint reductions through the use of renewable bio-resources are an appealing path to develop sustainable and economically viable green energy production. Biohydrogen production through biological processes is more eco-friendly. However lower yield of biohydrogenis due to the shift in metabolic pathways towards other products. This could be overcome by using nanomaterials with unique properties such as crystalline nature, stability, adsorption ability, catalytic properties, increased electroconductivity, and a high surface-to-volume ratio significantly enhances hydrogen generation. In this context, the review addresses the influence of nanomaterials for the production of biohydrogen. NPs interaction with bacteria, substrate, and enzyme changes were deeply studied for biotransformation properties in biohydrogen production. However, the biotransformation that occurs due to the presence of nanoparticles changes in molecular mechanisms of biohydrogen generation through the different biological processes that could be intensively studied.

Does temperature favour the spread of Raphidiopsis raciborskii, an invasive bloom-forming cyanobacterium, by altering cellular trade-offs?

As a tropical filamentous cyanobacterium, Raphidiopsis raciborskii has attracted much attention due to its expansion and toxin production. However, the mechanisms of its expansion to temperate regions have not been studied in detail. To address the potential strategies, the physiological and metabolomic profiles of R. raciborskii FACHB 1096 isolated from a temperate lake in China were determined and measured at different temperatures (10 °C, 15 °C, 20 °C, 25 °C, and 32 °C). The results demonstrated that temperature significantly changed cell viability, chlorophyll a content, specific growth rate, Chl a fluorescence, and filamentous shape of R. raciborskii. Low temperature decreased cell viability, specific growth rate, and photosynthetic efficiency, while the proportion of akinete and carbon fixation per unit cell were significantly increased compared with high temperature (32 °C). A constructed unimodal model indicated that filament length, cell volume, and cell length/width of R. raciborskii were significantly reduced in both high and low temperature environments. Under low-temperature conditions, R. raciborskii suffered different degrees of oxidative damage and produced corresponding antioxidant substances to resist oxidative stress, suggesting that low temperature changes the metabolic level of the cells, causing the cells to gradually switch from development to defense. Metabolomic data further confirmed that temperature change induced shifts in metabolic pathways in R. raciborskii, including starch and sucrose metabolic pathways, glutathione metabolic pathways, and the pentose phosphate pathways (PPP), as well as metabolic pathways related to the tricarboxylic acid (TCA) cycle. Our results indicated that the trade-offs of R. raciborskii cells among the growth, cell size, and metabolites can be significantly regulated by temperature, with broad implications for its global expansion in temperate waterbodies.

Insights into the shift of microbial community related to nitrogen cycle, especially N2O in vanadium-polluted soil

Soil is a vital contributor to the production of nitrous oxide (N2O), a potent greenhouse gas, through the nitrogen cycle, which can be influenced by accumulated vanadium (V) in soil but it is less pronounced. This work investigated the response of soil N2O fluxes along with major nitrogen cycle products (ammonium, nitrate, and nitrite) to different vanadium contents (0, 200, 500, 800, and 1100 mg V/kg), and the underlying microbial mechanisms. N2O fluxes was significantly influenced at high V content (1100 mg V/kg) due to its corresponding high water-soluble V content. Microbial composition and their correlations with nitrogen cycle products showed that microbes in dominant phyla (Actinobacteriota and Proteobacteria) and genus (Nocardioides, Lysobacter, Sphingomonas, and Marmoricola) might be the important contributor to N2O fluxes regardless of the V content. Moreover, high V contents (800, and 1100 mg V/kg) could enrich microbes involved in nitrogen cycle, but weaken their correlations with nitrogen-related products, such as in genus Bacillus, and change microbial correlation with N2O from associated with nitrate and nitrite to ammonium. Meanwhile, functional gene predication results showed that denitrifying genes nirKS and nosZ were negatively and positively correlated with V contents, respectively. These all further suggested that the shift of possible N2O metabolic pathways induced mainly by water-soluble V might be the underlying reason for N2O fluxes. These findings promote an understanding of the potential effect of metal pollution on N2O fluxes in soil.

Targeting Cancer Metabolism to Improve Outcomes with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors have revolutionized the treatment paradigm of several cancers. However, not all patients respond to treatment. Tumor cells reprogram metabolic pathways to facilitate growth and proliferation. This shift in metabolic pathways creates fierce competition with immune cells for nutrients in the tumor microenvironment and generates by-products harmful for immune cell differentiation and growth. In this review, we discuss these metabolic alterations and the current therapeutic strategies to mitigate these alterations to metabolic pathways that can be used in combination with checkpoint blockade to offer a new path forward in cancer management.

Bioplastic (PHBV) addition to soil alters microbial community structure and negatively affects plant-microbial metabolic functioning in maize

Microplastic contamination poses a significant threat to agroecosystem functioning, provoking a move away from the use of conventional oil-based plastics in agriculture, to biodegradable alternatives that may be degraded over a shorter timescale. The impact of these bioplastics on plant and soil health, however, has received relatively little attention. Here, we investigated the effect of soil loading (0.01%, 0.1%, 1% and 10%) of biobased microplastic poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) on soil and plant ( Zea mays L.) health and function. We showed that PHBV caused a dose-dependent reduction in plant growth and foliar nitrogen (N) content while untargeted metabolite analysis revealed significant shifts in foliar metabolic function. These results were also reflected in soil, where PHBV led to reduced plant availability of both ammonium and nitrate. Soil 14 C-isotope tracing and 16 S metabarcoding revealed that PHBV supressed microbial activity, reduced bacterial diversity and shifted microbial community structure, inducing a major shift in soil metabolic pathways, and thus functioning. Overall, our data suggests that the bioplastic PHBV is not environmentally benign and that contamination levels as low as 0.01% (0.01 mg kg -1 ) can induce significant short-term changes in both plant and soil microbial functioning, with potential implications for long term agroecosystem health. • Effect of biopolymer PHBV microplastic on soil and plant health was investigated • PHBV addition caused a dose-dependent negative effect on soil and plant health • PHBV addition altered foliar metabolism and reduced plant growth and foliar N • PHBV reduced soil microbial activity and changed the bacterial community structure • Bioplastics may not be environmentally benign

A Comprehensive Mechanistic Yeast Model Able to Switch Metabolism According to Growth Conditions

This paper proposes a general approach for building a mechanistic yeast model able to predict the shift of metabolic pathways. The mechanistic model accounts for the coexistence of several metabolic pathways (aerobic fermentation, glucose respiration, anaerobic fermentation and ethanol respiration) whose activation depends on growth conditions. This general approach is applied to a commercial strain of Saccharomyces cerevisiae. Stoichiometry and yeast kinetics were mostly determined from aerobic and completely anaerobic experiments. Known parameters were taken from the literature, and the remaining parameters were estimated by inverse analysis using the particle swarm optimization method. The optimized set of parameters allows the concentrations to be accurately determined over time, reporting global mean relative errors for all variables of less than 7 and 11% under completely anaerobic and aerobic conditions, respectively. Different affinities of yeast for glucose and ethanol tolerance under aerobic and anaerobic conditions were obtained. Finally, the model was successfully validated by simulating a different experiment, a batch fermentation process without gas injection, with an overall mean relative error of 7%. This model represents a useful tool for the control and optimization of yeast fermentation systems. More generally, the modeling framework proposed here is intended to be used as a building block of a digital twin of any bioproduction process.