-
Current Opinion in Immunology Oct 2023ERBIN and phosphoglucomutase 3 (PGM3) mutations both lead to rare primary atopic disorders characterized by allergic disease and connective tissue abnormalities, though... (Review)
Review
ERBIN and phosphoglucomutase 3 (PGM3) mutations both lead to rare primary atopic disorders characterized by allergic disease and connective tissue abnormalities, though each disorder has its own rather unique pattern of multisystem presentations. Pathway studies show how ERBIN mutations allow for enhanced TGFb signaling, and prevent STAT3 from negative-regulating TGFb signaling. This likely explains many elements of clinical overlap between disorders of STAT3 and TGFb signaling. The excessive TGFb signaling leading to increased IL-4 receptor expression also provides the rationale for precision-based therapy blocking the IL-4 receptor to treat the atopic disease. The mechanism by which PGM3 deficiency leads to atopic phenotypes is not well understood, nor is the broad variability in disease penetrance and expressivity, though preliminary studies suggest an overlap with IL-6 receptor signaling defects.
PubMed: 37369151
DOI: 10.1016/j.coi.2023.102353 -
International Journal of Molecular... Dec 2023Exogenous nitrogen and carbon can affect plant cell walls, which are composed of structural carbon. Sucrose synthase (SUS), invertase (INV), hexokinase (HXK),...
Exogenous nitrogen and carbon can affect plant cell walls, which are composed of structural carbon. Sucrose synthase (SUS), invertase (INV), hexokinase (HXK), phosphoglucomutase (PGM), and UDP-glucose pyrophosphorylase (UGP) are the key enzymes of sucrose metabolism involved in cell wall synthesis. To understand whether these genes are regulated by carbon and nitrogen to participate in structural carbon biosynthesis, we performed genome-wide identification, analyzed their expression patterns under different carbon and nitrogen treatments, and conducted preliminary functional verification. Different concentrations of nitrogen and carbon were applied to poplar ( Torr. and Gray), which caused changes in cellulose, lignin, and hemicellulose contents. In poplar, 6 s, 20 s, 6 s, 4 s, and 2 s were identified. Moreover, the physicochemical properties, collinearity, and tissue specificity were analyzed. The correlation analysis showed that the expression levels of /, ////, , , /, /, and were positively correlated with the cellulose content. Meanwhile, the knockout of significantly reduced the cellulose content. This study could lay the foundation for revealing the functions of s, s, s, , and s, which affected structural carbon synthesis regulated by nitrogen and carbon, proving that is involved in cell wall synthesis.
Topics: Populus; Cellulose; Lignin; Carbon; Nitrogen; Gene Expression Regulation, Plant
PubMed: 38139109
DOI: 10.3390/ijms242417277 -
International Journal of Biological... Dec 2023Exopolysaccharides (EPS) produced by microorganisms play a vital role in physiological and ecological processes. However, the mechanisms of EPS synthesis and release in...
Exopolysaccharides (EPS) produced by microorganisms play a vital role in physiological and ecological processes. However, the mechanisms of EPS synthesis and release in anaerobic environments remain poorly understood. Here, we provide the first evidence of anaerobic EPS synthesis by the fungus Schizophyllum commune 20R-7-F01, isolated from coal-bearing sediments ~2.0 km below the seafloor. Under anaerobic conditions, the fungus exhibited significantly higher specific EPS production (1.57 times) than under aerobic conditions. Transcriptomic analysis revealed 2057 differentially expressed genes (DEGs) in the strain cultured anaerobically for 7 days compared to aerobically. Among these genes, 642 were significantly upregulated, while 1415 were significantly downregulated, mainly associated with carbon metabolism pathways. Genes involved in glycolysis and EPS synthesis, including hexokinase (HK), phosphoglucomutase (PGM), and (1 → 3)-β-glucan synthase (GLS), were significantly upregulated, while those related to the TCA cycle, respiratory chain, and pentose phosphate pathway were downregulated under anaerobic conditions. These findings highlight the oxygen-dependent regulation of EPS synthesis and suggest that EPS may serve as a key mechanism for fungal adaptation to anaerobic environments.
Topics: Schizophyllum; Anaerobiosis; Glycolysis; beta-Glucans
PubMed: 37820905
DOI: 10.1016/j.ijbiomac.2023.127339 -
Poultry Science Jan 2024Avian coccidiosis caused by Eimeria is a serious parasitic disease that poses a threat to the poultry industry. Currently, prevention and treatment mainly rely on the...
Avian coccidiosis caused by Eimeria is a serious parasitic disease that poses a threat to the poultry industry. Currently, prevention and treatment mainly rely on the administration of anticoccidials and live oocyst vaccines. However, the prevalence of drug resistance and the inherent limitations of live vaccines have driven the development of novel vaccines. In this study, the surface protein (Et-SAG14), a previously annotated rhoptry protein (Eten5-B), and a gametocyte phosphoglucomutase (Et-PGM1) were characterized and the vaccine potential of the recombinant proteins were evaluated. Et-SAG14 was dispersed in the form of particles in the sporozoite and merozoite stages, whereas Et-PGM1 was distributed in the apical part of the sporozoite and merozoite stages. The previously annotated rhoptry Eten5-B was found not to be located in the rhoptry but distributed in the cytoplasm of sporozoites and merozoites. Immunization with rEten5-B significantly elevated host interferon gamma (IFN-γ) and interleukin 10 (IL-10) transcript levels and exhibited moderate anticoccidial effects with an anticoccidial index (ACI) of 161. Unexpectedly, both recombinant Et-SAG14 and Et-PGM1 immunization significantly reduced host IFN-γ and IL-10 transcription levels, and did not show protection against E. tenella challenge (ACI < 80). These results suggest that the rEten5-B protein can trigger immune protection against E. tenella and may be a potential and effective subunit vaccine for the control of coccidiosis in poultry.
Topics: Animals; Eimeria tenella; Interleukin-10; Chickens; Recombinant Proteins; Coccidiosis; Sporozoites; Interferon-gamma; Vaccines; Poultry Diseases; Protozoan Vaccines
PubMed: 37980744
DOI: 10.1016/j.psj.2023.103234 -
Journal of Microbiology and... May 2024Glucosylation is a well-known approach to improve the solubility, pharmacological, and biological properties of flavonoids, making flavonoid glucosides a target for...
Glucosylation is a well-known approach to improve the solubility, pharmacological, and biological properties of flavonoids, making flavonoid glucosides a target for large-scale biosynthesis. However, the low yield of products coupled with the requirement of expensive UDP-sugars limits the application of enzymatic systems for large-scale. is a Gram-positive and generally regarded as safe (GRAS) bacteria frequently employed for the large-scale production of amino acids and bio-fuels. Due to the versatility of its cell factory system and its non-endotoxin producing properties, it has become an attractive system for the industrial-scale biosynthesis of alternate products. Here, we explored the cell factory of for efficient glucosylation of flavonoids using apigenin as a model flavonoid, with the heterologous expression of a promiscuous glycosyltransferase, YdhE from and the endogenous overexpression of genes encoding UDP-glucose pyrophosphorylase and encoding phosphoglucomutase involved in the synthesis of UDP-glucose to create a cell factory system capable of efficiently glucosylation apigenin with a high yield of glucosides production. Consequently, the production of various apigenin glucosides was controlled under different temperatures yielding almost 4.2 mM of APG1(apigenin-4'-O-β-glucoside) at 25°C, and 0.6 mM of APG2 (apigenin-7-O-β-glucoside), 1.7 mM of APG3 (apigenin-4',7-O-β-diglucoside) and 2.1 mM of APG4 (apigenin-4',5-O-β-diglucoside) after 40 h of incubation with the supplementation of 5 mM of apigenin and 37°C. The cost-effective developed system could be used to modify a wide range of plant secondary metabolites with increased pharmacokinetic activities on a large scale without the use of expensive UDP-sugars.
Topics: Corynebacterium glutamicum; Apigenin; Metabolic Engineering; Glucosides; Glycosylation; Bacillus licheniformis; Uridine Diphosphate Glucose; Bacterial Proteins; UTP-Glucose-1-Phosphate Uridylyltransferase; Glycosyltransferases
PubMed: 38563097
DOI: 10.4014/jmb.2401.01017 -
Frontiers in Veterinary Science 2023Inosine monophosphate (IMP) is naturally present in poultry muscle and plays a key role in improving meat flavour. However, IMP deposition is regulated by numerous genes...
BACKGROUND
Inosine monophosphate (IMP) is naturally present in poultry muscle and plays a key role in improving meat flavour. However, IMP deposition is regulated by numerous genes and complex molecular networks. In order to excavate key candidate genes that may regulate IMP synthesis, we performed proteome and metabolome analyses on the leg muscle, compared to the breast muscle control of 180-day-old Jingyuan chickens (hens), which had different IMP content. The key candidate genes identified by a differential analysis were verified to be associated with regulation of IMP-specific deposition.
RESULTS
The results showed that the differentially expressed (DE) proteins and metabolites jointly involve 14 metabolic pathways, among which the purine metabolic pathway closely related to IMP synthesis and metabolism is enriched with four DE proteins downregulated (with higher expression in breast muscles than in leg muscles), including adenylate kinase 1 (), adenosine monophosphate deaminase 1 (), pyruvate kinase muscle isoenzyme 2 () and phosphoglucomutase 1 (), six DE metabolites, Hypoxanthine, Guanosine, L-Glutamine, AICAR, AMP and Adenylsuccinic acid. Analysis of gene showed that the high expression of promoted the proliferation and differentiation of myoblasts and inhibited the apoptosis of myoblasts. ELISA tests have shown that reduced adenosine triphosphate (ATP) and IMP and uric acid (UA), while enhancing the biosynthesis of hypoxanthine (HX). In addition, up-regulation of inhibited the expression of purine metabolism pathway related genes, and promoted the IMP and salvage synthesis pathways.
CONCLUSION
This study preliminarily explored the mechanism of action of in regulating the growth and development of myoblasts and specific IMP deposition in Jingyuan chickens, which provided certain theoretical basis for the development and utilization of excellent traits in Jingyuan chickens.
PubMed: 38164393
DOI: 10.3389/fvets.2023.1276582 -
Journal of Plant Physiology May 2024Roots exhibit hydrotropism in response to moisture gradients, with the hydrotropism-related gene Mizu-kussei1 (MIZ1) playing a role in regulating root hydrotropism in an...
Roots exhibit hydrotropism in response to moisture gradients, with the hydrotropism-related gene Mizu-kussei1 (MIZ1) playing a role in regulating root hydrotropism in an oblique orientation. However, the mechanisms underlying MIZ1-regulated root hydrotropism are not well understood. In this study, we employed obliquely oriented experimental systems to investigate root hydrotropism in Arabidopsis. We found that the miz1 mutant displays reduced root hydrotropism but increased root gravitropism following hydrostimulation, as compared to wild-type plants. Conversely, overexpression of AtMIZ1 leads to enhanced root hydrotropism but decreased root gravitropism following hydrostimulation, as compared to wild-type plants. Using co-immunoprecipitation followed by mass spectrometry (IP-MS), we explored proteins that interact with AtMIZ1, and we identified PGMC1 co-immunoprecipitated with MIZ1 in vivo. Furthermore, the miz1 mutant exhibited higher expression of the PGMC1 gene and increased phosphoglucomutase (PGM) activity, while AtMIZ1 overexpressors resulted in lower expression of the PGMC1 gene, reduced amyloplast amount, and reduced PGM activity in comparison to wild-type roots. In addition, different Arabidopsis natural accessions having difference in their hydrotropic response demonstrated expression level of PGMC1 was negatively correlated with hydrotropic root curvature and AtMIZ1 expression. Our results provide valuable insights into the role of amyloplast in MIZ1-regulated root hydrotropism.
Topics: Arabidopsis; Arabidopsis Proteins; Water; Tropism; Gravitropism; Plant Roots
PubMed: 38507925
DOI: 10.1016/j.jplph.2024.154224 -
Biotechnology For Biofuels and... Nov 2023Yarrowia lipolytica, one of the most charming chassis cells in synthetic biology, is unable to use xylose and cellodextrins.
Installing xylose assimilation and cellodextrin phosphorolysis pathways in obese Yarrowia lipolytica facilitates cost-effective lipid production from lignocellulosic hydrolysates.
BACKGROUND
Yarrowia lipolytica, one of the most charming chassis cells in synthetic biology, is unable to use xylose and cellodextrins.
RESULTS
Herein, we present work to tackle for the first time the engineering of Y. lipolytica to produce lipids from cellodextrins and xylose by employing rational and combinatorial strategies. This includes constructing a cellodextrin-phosphorolytic Y. lipolytica by overexpressing Neurospora crassa cellodextrin transporter, Clostridium thermocellum cellobiose/cellodextrin phosphorylase and Saccharomyces cerevisiae phosphoglucomutase. The effect of glucose repression on xylose consumption was relieved by installing a xylose uptake facilitator combined with enhanced PPP pathway and increased cytoplasmic NADPH supply. Further enhancing lipid production and interrupting its consumption conferred the obese phenotype to the engineered yeast. The strain is able to co-ferment glucose, xylose and cellodextrins efficiently, achieving a similar μ of 0.19 h, a q of 0.34 g-s/g-DCW/h and a Y of 0.54 DCW-g/g-s on these substrates, and an accumulation of up to 40% of lipids on the sugar mixture and on wheat straw hydrolysate.
CONCLUSIONS
Therefore, engineering Y. lipolytica capable of assimilating xylose and cellodextrins is a vital step towards a simultaneous saccharification and fermentation (SSF) process of LC biomass, allowing improved substrate conversion rate and reduced production cost due to low demand of external glucosidase.
PubMed: 38031183
DOI: 10.1186/s13068-023-02434-9 -
Biochemistry Jun 2024-linked congenital disorder of glycosylation (PGM1-CDG) is an autosomal recessive disease characterized by several phenotypes, some of which are life-threatening....
-linked congenital disorder of glycosylation (PGM1-CDG) is an autosomal recessive disease characterized by several phenotypes, some of which are life-threatening. Research focusing on the disease-related variants of the α-D-phosphoglucomutase 1 (PGM1) protein has shown that several are insoluble in vitro and expressed at low levels in patient fibroblasts. Due to these observations, we hypothesized that some disease-linked PGM1 protein variants are structurally destabilized and subject to protein quality control (PQC) and rapid intracellular degradation. Employing yeast-based assays, we show that a disease-associated human variant, PGM1 L516P, is insoluble, inactive, and highly susceptible to ubiquitylation and rapid degradation by the proteasome. In addition, we show that PGM1 L516P forms aggregates in and that both the aggregation pattern and the abundance of PGM1 L516P are chaperone-dependent. Finally, using computational methods, we perform saturation mutagenesis to assess the impact of all possible single residue substitutions in the PGM1 protein. These analyses identify numerous missense variants with predicted detrimental effects on protein function and stability. We suggest that many disease-linked PGM1 variants are subject to PQC-linked degradation and that our in silico site-saturated data set may assist in the mechanistic interpretation of PGM1 variants.
Topics: Humans; Phosphoglucomutase; Saccharomyces cerevisiae; Proteolysis; Mutation, Missense; Ubiquitination; Congenital Disorders of Glycosylation; Protein Stability; Proteasome Endopeptidase Complex
PubMed: 38743592
DOI: 10.1021/acs.biochem.4c00042