PubMed

Bioresour Technol. 2023 Sep 9:129755. doi: 10.1016/j.biortech.2023.129755. Online ahead of print.ABSTRACTThe nitrate nitrogen removal characteristics of Pseudomonas JI-2 under strong alkaline conditions and the composition and functional groups of extracellular polymeric substance were analyzed. Furthermore, nontargeted metabonomics and bioinformatics technology were used to investigate the alkaline tolerance mechanism. JI-2 removed 11.05 mg N/(L·h) of nitrate with the initial pH, C/N and temperature were 11.0, 8 and 25 °C respectively. Even when the pH was maintained at 11.0, JI-2 could still effectively remove nitrate. JI-2 contains a large number of Na+/H+ antiporters, such as Mrp, Mnh (mnhACDEFG) and Pha (phaACDEFG), which can stabilize the intracellular acid-base environment, and SlpA can enable quick adaptation to alkaline conditions. Moreover, JI-2 responds to the strong alkaline environment by secreting more polysaccharides, acidic functional groups and compatible solutes and regulating key metabolic processes such as pantothenate and CoA biosynthesis and carbapenem biosynthesis. Therefore, JI-2 can survive in strong alkaline environments and remove nitrate efficiently.PMID:37696334 | DOI:10.1016/j.biortech.2023.129755

Psychoneuroendocrinology. 2023 Sep 9;158:106380. doi: 10.1016/j.psyneuen.2023.106380. Online ahead of print.ABSTRACTOBJECTIVE: Stress is common among pregnant individuals and is associated with an altered gut microbiota composition in infants. It is unknown if these compositional changes persist into the preschool years when the gut microbiota reaches an adult-like composition. This study aimed to investigate if indicators of prenatal stress (i.e., psychological distress and stress-related physiology) are associated with children's gut microbiota composition and metabolites at 3-4 years of age.METHODS: Maternal-child pairs (n = 131) were from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. Each trimester, psychological distress was measured as symptoms of anxiety (Symptom Checklist-90-R) and depressed mood (Edinburgh Postnatal Depression Scale), whereas salivary cortisol was quantified as a measure of stress-related physiology. Child stool samples were collected at 3-4 years to evaluate gut microbiota composition using 16S rRNA gene sequencing and fecal metabolome using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Associations between prenatal distress and cortisol with the gut microbiota were determined using Pearson and Spearman correlations and corrected for multiple testing. Associations between prenatal distress and cortisol with the fecal metabolome were assessed using Metaboanalyst.RESULTS: Symptoms of depressed mood during the 2nd and 3rd trimesters and anxiety during the 2nd trimester of pregnancy were associated with increased alpha diversity of the child's gut microbiota. Cortisol levels during the 1st trimester were also associated with increased Faith PD diversity (r = 0.32), whereas cortisol levels during the 2nd trimester were associated with reduced Shannon diversity (r = -0.27). Depression scores during the 2nd and 3rd trimesters were associated with reductions in the relative abundances of Eggerthella, Parasutterella, and increases in Ruminococcaceae (rs = -0.28, rs = -0.32, rs = 0.32, respectively), as well as the fecal metabolome (e.g., branched-chain amino acid metabolism). Cortisol levels during the 2nd trimester correlated with 7 bacterial taxa, whereas 1st-trimester cortisol levels were associated with the child's fecal metabolome.CONCLUSIONS: Prenatal distress and cortisol were associated with both child gut microbiota composition and fecal metabolome at preschool age. Understanding these associations may allow for the identification of microbiota-targeted interventions to support child developmental outcomes affected by prenatal stress.PMID:37696229 | DOI:10.1016/j.psyneuen.2023.106380

J Pharm Biomed Anal. 2023 Sep 4;236:115693. doi: 10.1016/j.jpba.2023.115693. Online ahead of print.ABSTRACTFuzi decoction (FZD) is clinically used to treat chronic heart failure (CHF) in China, but the mechanism underlying FZD treatment in CHF remains unclear. Here, we investigated the potential mechanism underlying FZD treatment of CHF in rats. First, the compounds in FZD-containing serum of rats were identified, and 16 S rRNA sequencing and GC-MS-based untargeted metabolomics analysis were then performed. The levels of fecal short-chain fatty acids (SCFAs) were determined and compared, and fecal microbiota transplantation (FMT) was used to verify the role of the gut microbiota. Our results identified 27 in FD-containing serum. FZD increased the Firmicutes-to-Bacteroidetes ratio and the Lactobacillus abundance and affected the β diversity of the gut microbiota in rats with CHF. Differential species analysis showed that Lactobacillus and Prevotella were biomarkers of FZD treatment of CHF. Untargeted metabolomics analysis revealed that FZD affected valine, leucine and isoleucine biosynthesis; galactose metabolism; and aminoacyl-tRNA biosynthesis in rats with CHF. Furthermore, FZD significantly increased the acetic acid, propionic acid, butyric acid and isopentanoic acid levels in the feces of rats with CHF. Correlation analysis showed that the butyric acid and Lactobacillus levels had the strongest correlation in the control, sham and high-dose FZD (HFZD) groups, and many microbiota components were closely related to differentially abundant metabolites. FMT revealed that the fecal microbiota obtained from the HFZD group changed the heart rate; the brain natriuretic peptide (BNP), acetic acid, propionic acid, butyric acid, and metabolite levels; and the gut microbiota in rats with CHF. In summary, our study revealed that the mechanism of action of FZD in CHF treatment may be related to improvements in the gut microbiota, elevations in the SCFA content and the regulation of valine, leucine, and isoleucine biosynthesis; galactose metabolism; and other metabolic pathways.PMID:37696191 | DOI:10.1016/j.jpba.2023.115693

Comput Biol Med. 2023 Aug 29;165:107425. doi: 10.1016/j.compbiomed.2023.107425. Online ahead of print.ABSTRACTDuring the last decade, genomic, transcriptomic, proteomic, metabolomic, and other omics datasets have been generated for a wide range of marine organisms, and even more are still on the way. Marine organisms possess unique and diverse biosynthetic pathways contributing to the synthesis of novel secondary metabolites with significant bioactivities. As marine organisms have a greater tendency to adapt to stressed environmental conditions, the chance to identify novel bioactive metabolites with potential biotechnological application is very high. This review presents a comprehensive overview of the available "-omics" and "multi-omics" approaches employed for characterizing marine metabolites along with novel data integration tools. The need for the development of machine-learning algorithms for "multi-omics" approaches is briefly discussed. In addition, the challenges involved in the analysis of "multi-omics" data and recommendations for conducting "multi-omics" study were discussed.PMID:37696182 | DOI:10.1016/j.compbiomed.2023.107425

Food Chem. 2023 Sep 9;434:137360. doi: 10.1016/j.foodchem.2023.137360. Online ahead of print.ABSTRACTSulfur treatment for the pesticidal and antibacterial processing of food products has been criticized since it impairs the quality of treated products. The inspection of sulfur-treated products is thus required to achieve the regulation of sulfur treatment. Sulfite assay is currently available for the inspection, but it bears the disadvantages of inaccurate results and complex experimental procedures. Here we report a new chemical marker, namely tryptophan sulfonate, that can be used for the accurate and efficient inspection of sulfur-treated foods. First, the marker was discovered in sulfur-fumigated ginger, yam, and ginseng by untargeted metabolomics. The marker identity was then elucidated using chromatographic separation, nuclear magnetic resonance analysis and chemical synthesis. Finally, to demonstrate its applicability in the inspection, a tryptophan sulfonate assay was developed to test 50 commercial food samples, and the results indicated that it performed better than the sulfite assay in terms of both accuracy and efficiency.PMID:37696151 | DOI:10.1016/j.foodchem.2023.137360

J Chromatogr A. 2023 Aug 31;1708:464342. doi: 10.1016/j.chroma.2023.464342. Online ahead of print.ABSTRACTThe importance of lipids seen in studies of metabolism, cancer, the recent COVID-19 pandemic and other diseases has brought the field of lipidomics to the forefront of clinical research. Quantitative and comprehensive analysis is required to understand biological interactions among lipid species. However, lipidomic analysis is often challenging due to the various compositional structures, diverse physicochemical properties, and wide dynamic range of concentrations of lipids in biological systems. To study the comprehensive lipidome, a hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS)-based screening method with 1200 lipid features across 19 (sub)classes, including both nonpolar and polar lipids, has been developed. HILIC-MS/MS was selected due to its class separation property and fatty acyl chain level information. 3D models of class chromatographic retention behavior were established and evaluations of cross-class and within-class interferences were performed to avoid over-reporting these features. This targeted HILIC-MS/MS method was fully validated, with acceptable analytical parameters in terms of linearity, precision, reproducibility, and recovery. The accurate quantitation of 608 lipid species in the SRM 1950 NIST plasma was achieved using multi-internal standards per class and post-hoc correction, extending current databases by providing lipid concentrations resolved at fatty acyl chain level. The overall correlation coefficients (R2) of measured concentrations with values from literature range from 0.64 to 0.84. The applicability of the developed targeted lipidomics method was demonstrated by discovering 520 differential lipid features related to COVID-19 severity. This high coverage and targeted approach will aid in future investigations of the lipidome in various disease contexts.PMID:37696124 | DOI:10.1016/j.chroma.2023.464342

Orphanet J Rare Dis. 2023 Sep 11;18(1):282. doi: 10.1186/s13023-023-02900-5.ABSTRACTBACKGROUND: Wilson's disease (WD) is a hereditary disorder that results in the accumulation of copper. The pathogenic mechanism is not well understood, and diagnosing the disease can be challenging, as it shares similarities with more prevalent conditions. To explore the metabolomic features of WD and differentiate it from other diseases related to copper metabolism, we conducted targeted and untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS). We compared the metabolomic profiles of two subgroups of WD patients, namely hepatic WD (H-WD) and neurological WD (N-WD), H-WD patients and liver cirrhosis patients (who exhibit similar symptoms but have normal copper levels), and N-WD patients and Parkinson's disease patients (who exhibit similar symptoms but have normal copper levels).RESULTS: Our pairwise comparisons revealed distinct metabolomic profiles for male and female WD patients, H-WD and N-WD patients, N-WD and Parkinson's disease patients, and H-WD and liver cirrhosis patients. We then employed logistic regression analysis, receiver operating characteristic (ROC) analysis, and model construction to identify candidate diagnostic biomarkers that differentiate H-WD from liver cirrhosis and N-WD from Parkinson's disease. Based on the spatial distribution of data obtained via PLS-DA analysis, we discovered variations in hydrophilic metabolites (aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; arginine biosynthesis; and nicotinate and nicotinamide) and lipophilic metabolites (TG(triglyceride) (16:0_16:1_22:6), TG (16:0_16:0_22:6), and TG (16:0_16:1_22:5)) between H-WD and N-WD. Moreover, WD patients display metabolic traits that distinguish it from comparable conditions (liver cirrhosis and Parkinson's disease).CONCLUSIONS: Our analysis reveals significant variations in the levels of metabolites in critical metabolic pathways and numerous lipids in WD.ROC analysis indicates that three metabolites may be considered as candidate biomarkers for diagnosing WD.PMID:37697371 | DOI:10.1186/s13023-023-02900-5

BMC Genomics. 2023 Sep 11;24(1):537. doi: 10.1186/s12864-023-09567-z.ABSTRACTBACKGROUND: The mechanism of grain development in elite maize breeding lines has not been fully elucidated. Grain length, grain width and grain weight are key components of maize grain yield. Previously, using the Chinese elite maize breeding line Chang7-2 and its large grain mutant tc19, we characterized the grain size developmental difference between Chang7-2 and tc19 and performed transcriptomic analysis.RESULTS: In this paper, using Chang7-2 and tc19, we performed comparative transcriptomic, proteomic and metabolomic analyses at different grain development stages. Through proteomics analyses, we found 2884, 505 and 126 differentially expressed proteins (DEPs) at 14, 21 and 28 days after pollination, respectively. Through metabolomics analysis, we identified 51, 32 and 36 differentially accumulated metabolites (DAMs) at 14, 21 and 28 days after pollination, respectively. Through multiomics comparative analysis, we showed that the phenylpropanoid pathways are influenced at transcriptomic, proteomic and metabolomic levels in all the three grain developmental stages.CONCLUSION: We identified several genes in phenylpropanoid biosynthesis, which may be related to the large grain phenotype of tc19. In summary, our results provided new insights into maize grain development.PMID:37697229 | DOI:10.1186/s12864-023-09567-z

Mikrochim Acta. 2023 Sep 11;190(10):381. doi: 10.1007/s00604-023-05974-x.ABSTRACTMnO2 nanosheets (MnO2NSs) were synthesized by one-step method, and MnO2NSs were applied to A549 cell chemodynamic Therapy (CDT). The cytotoxicity, redox ability, and reactive oxygen species production of MnO2NSs have been investigated, and differences in cell metabolism during CDT were determined using liquid chromatography-mass spectrometry (LC-MS/MS). In addition, the metabolites of A549 lung cancer cells affected by MnO2NSs treatment are identified; metabolite differences were identified by PCA, PLS-DA, orthogonal PLS-DA, and other methods; and these differences were analyzed using non-targeted metabolomics. We found that A549 cells which were treated by MnO2NSs have 17 different metabolites and 9 metabolic pathways that varied markedly. Owing to their unique composition, structure, and physicochemical properties, MnO2NSs and their composites have become a favored type of nanomaterial used for CDT in cancer therapy. This work provides insights into the mechanism underlying the effects of MnO2NSs on the tumor microenvironment of A549 lung cancer cells, effectively making up for the deficiency of the study on cellular mechanism of CDT-induced apoptosis of cancer cells. It could aid the development of cancer CDT treatment strategies and help improve the use of nanomaterials in the clinical field.PMID:37697041 | DOI:10.1007/s00604-023-05974-x

Sci Rep. 2023 Sep 11;13(1):14940. doi: 10.1038/s41598-023-42363-z.ABSTRACTTo explore potential metabolomics biomarkers in predicting post-herpetic neuralgia (PHN) induced by herpes zoster (HZ). A total of 90 eligible patients were prospectively enrolled and assigned into an acute pain (ACP) group and a PHN group. Serum samples were collected before clinical intervention to perform metabolomics profiling analyses using gas chromatography mass spectrometry (GC-MS). Key metabolites were identified using partial least squares discriminant analysis (PLS-DA). A binary logistic regression was used to build a combined biomarker model to predict PHN from ACP. The discriminating efficiency of the combined biomarker model was investigated and validated by internal validation. Six metabolites were identified as the key metabolites related to PHN. All these metabolites (N-Acetyl-5-hydroxytryptaMine, glucose, dehydroascorbic acid, isopropyl-beta-D-thiogalactopyranoside, 1,5-anhydro-D-sorbitol, and glutamic acid) were found elevated in the PHN group. Pathway analyses showed that glucose-alanine cycle, tryptophan metabolism, tyrosine metabolism, lactose degradation, malate-aspartate shuttle were top five metabolic pathways evolved in PHN. The AUC was 0.85 (95% CI 0.76-0.93) for the combined biomarker model, and was 0.91 (95% CI 0.84-1.00) for the internal validation data set to predict PHN. Metabolomics analyses of key metabolites could be used to predict PHN induced by HZ.PMID:37697028 | DOI:10.1038/s41598-023-42363-z

Commun Biol. 2023 Sep 11;6(1):931. doi: 10.1038/s42003-023-05307-x.ABSTRACTThe transition from deep dormancy to seed germination is essential for the life cycle of plants, but how this process occurs in the gymnosperm Chinese yew (Taxus chinensis var mairei), the natural source of the anticancer drug paclitaxel, remains unclear. Herein, we analyse the transcriptome, proteome, spatial metabolome, and spatial lipidome of the Chinese yew and present the multi-omics profiles of dormant and germinating seeds. Our results show that abscisic acid and gibberellic acid 12 homoeostasis is closely associated with gene transcription and protein translation, and the balance between these phytohormones thereby determines if seeds remain dormant or germinate. We find that an energy supply of carbohydrates from glycolysis and the TCA cycle feed into the pentose phosphate pathway during seed germination, and energy supplied from lipids are mainly derived from the lipolysis of triacylglycerols. Using mass spectrometry imaging, we demonstrate that the spatial distribution of plant hormones and phospholipids has a remarkable influence on embryo development. We also provide an atlas of the spatial distribution of paclitaxel C in Chinese yew seeds for the first time. The data from this study enable exploration of the germination mechanism of Chinese yew seeds across several omics levels.PMID:37697020 | DOI:10.1038/s42003-023-05307-x

Sci Rep. 2023 Sep 11;13(1):14999. doi: 10.1038/s41598-023-41819-6.ABSTRACTThis study differentiates myocardial infarction (MI) and strangulation death (STR) from the perspective of amino acid metabolism. In this study, MI mice model via subcutaneous injection of isoproterenol and STR mice model by neck strangulation were constructed, and were randomly divided into control (CON), STR, mild MI (MMI), and severe MI (SMI) groups. The metabolomics profiles were obtained by liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics. Principal component analysis, partial least squares-discriminant analysis, volcano plots, and heatmap were used for discrepancy metabolomics analysis. Pathway enrichment analysis was performed and the expression of proteins related to metabolomics was detected using immunohistochemical and western blot methods. Differential metabolites and metabolite pathways were screened. In addition, we found the expression of PPM1K was significantly reduced in the MI group, but the expression of p-mTOR and p-S6K1 were significantly increased (all P < 0.05), especially in the SMI group (P < 0.01). The expression of Cyt-C was significantly increased in each group compared with the CON group, especially in the STR group (all P < 0.01), and the expression of AMPKα1 was significantly increased in the STR group (all P < 0.01). Our study for the first time revealed significant differences in amino acid metabolism between STR and MI.PMID:37696922 | DOI:10.1038/s41598-023-41819-6

Sci Rep. 2023 Sep 11;13(1):15001. doi: 10.1038/s41598-023-42093-2.ABSTRACTGlobally, bread wheat (Triticum aestivum) is one of the most important staple foods; when exposed to drought, wheat yields decline. Although much research has been performed to generate higher yield wheat cultivars, there have been few studies on improving end-product quality under drought stress, even though wheat is processed into flour to produce so many foods, such as bread, noodles, pancakes, cakes, and cookies. Recently, wheat cultivation has been affected by severe drought caused by global climate change. In previous studies, seed shrinkage was observed in wheat exposed to continuous drought stress during seed development. In this study, we investigated how progressive drought stress affected seed development by metabolomic and transcriptomic analyses. Metabolite profiling revealed the drought-sensitive line reduced accumulation of proline and sugar compared with the water-saving, drought-tolerant transgenic line overexpressing the abscisic acid receptor TaPYL4 under drought conditions in spikelets with developing seeds. Meanwhile, the expressions of genes involved in translation, starch biosynthesis, and proline and arginine biosynthesis was downregulated in the drought-sensitive line. These findings suggest that seed shrinkage, exemplifying a deficiency in endosperm, arose from the hindered biosynthesis of crucial components including seed storage proteins, starch, amino acids, and sugars, ultimately leading to their inadequate accumulation within spikelets. Water-saving drought tolerant traits of wheat would aid in supporting seed formation under drought conditions.PMID:37696863 | DOI:10.1038/s41598-023-42093-2

Nat Commun. 2023 Sep 11;14(1):5595. doi: 10.1038/s41467-023-41351-1.ABSTRACTDownregulation of endothelial Sirtuin1 (Sirt1) in insulin resistant states contributes to vascular dysfunction. Furthermore, Sirt1 deficiency in skeletal myocytes promotes insulin resistance. Here, we show that deletion of endothelial Sirt1, while impairing endothelial function, paradoxically improves skeletal muscle insulin sensitivity. Compared to wild-type mice, male mice lacking endothelial Sirt1 (E-Sirt1-KO) preferentially utilize glucose over fat, and have higher insulin sensitivity, glucose uptake, and Akt signaling in fast-twitch skeletal muscle. Enhanced insulin sensitivity of E-Sirt1-KO mice is transferrable to wild-type mice via the systemic circulation. Endothelial Sirt1 deficiency, by inhibiting autophagy and activating nuclear factor-kappa B signaling, augments expression and secretion of thymosin beta-4 (Tβ4) that promotes insulin signaling in skeletal myotubes. Thus, unlike in skeletal myocytes, Sirt1 deficiency in the endothelium promotes glucose homeostasis by stimulating skeletal muscle insulin sensitivity through a blood-borne mechanism, and augmented secretion of Tβ4 by Sirt1-deficient endothelial cells boosts insulin signaling in skeletal muscle cells.PMID:37696839 | DOI:10.1038/s41467-023-41351-1

Proc Natl Acad Sci U S A. 2023 Sep 19;120(38):e2218150120. doi: 10.1073/pnas.2218150120. Epub 2023 Sep 11.ABSTRACTThe endothelium is a major target of the proinflammatory cytokine, tumor necrosis factor alpha (TNFα). Exposure of endothelial cells (EC) to proinflammatory stimuli leads to an increase in mitochondrial metabolism; however, the function and regulation of elevated mitochondrial metabolism in EC in response to proinflammatory cytokines remain unclear. Studies using high-resolution metabolomics and 13C-glucose and 13C-glutamine labeling flux techniques showed that pyruvate dehydrogenase activity (PDH) and oxidative tricarboxylic acid cycle (TCA) flux are elevated in human umbilical vein ECs in response to overnight (16 h) treatment with TNFα (10 ng/mL). Mechanistic studies indicated that TNFα mediated these metabolic changes via mitochondrial-specific protein degradation of pyruvate dehydrogenase kinase 4 (PDK4, inhibitor of PDH) by the Lon protease via an NF-κB-dependent mechanism. Using RNA sequencing following siRNA-mediated knockdown of the catalytically active subunit of PDH, PDHE1α (PDHA1 gene), we show that PDH flux controls the transcription of approximately one-third of the genes that are up-regulated by TNFα stimulation. Notably, TNFα-induced PDH flux regulates a unique signature of proinflammatory mediators (cytokines and chemokines) but not inducible adhesion molecules. Metabolomics and ChIP sequencing for acetylated modification on lysine 27 of histone 3 (H3K27ac) showed that TNFα-induced PDH flux promotes histone acetylation of specific gene loci via citrate accumulation and ATP-citrate lyase-mediated generation of acetyl CoA. Together, these results uncover a mechanism by which TNFα signaling increases oxidative TCA flux of glucose to support TNFα-induced gene transcription through extramitochondrial acetyl CoA generation and histone acetylation.PMID:37695914 | DOI:10.1073/pnas.2218150120

Proc Natl Acad Sci U S A. 2023 Sep 19;120(38):e2302489120. doi: 10.1073/pnas.2302489120. Epub 2023 Sep 11.ABSTRACTLoss of estrogen receptor (ER) pathway activity promotes breast cancer progression, yet how this occurs remains poorly understood. Here, we show that serine starvation, a metabolic stress often found in breast cancer, represses estrogen receptor alpha (ERα) signaling by reprogramming glucose metabolism and epigenetics. Using isotope tracing and time-resolved metabolomic analyses, we demonstrate that serine is required to maintain glucose flux through glycolysis and the TCA cycle to support acetyl-CoA generation for histone acetylation. Consequently, limiting serine depletes histone H3 lysine 27 acetylation (H3K27ac), particularly at the promoter region of ER pathway genes including the gene encoding ERα, ESR1. Mechanistically, serine starvation impairs acetyl-CoA-dependent gene expression by inhibiting the entry of glycolytic carbon into the TCA cycle and down-regulating the mitochondrial citrate exporter SLC25A1, a critical enzyme in the production of nucleocytosolic acetyl-CoA from glucose. Consistent with this model, total H3K27ac and ERα expression are suppressed by SLC25A1 inhibition and restored by acetate, an alternate source of acetyl-CoA, in serine-free conditions. We thus uncover an unexpected role for serine in sustaining ER signaling through the regulation of acetyl-CoA metabolism.PMID:37695911 | DOI:10.1073/pnas.2302489120

Proc Natl Acad Sci U S A. 2023 Sep 19;120(38):e2305575120. doi: 10.1073/pnas.2305575120. Epub 2023 Sep 11.ABSTRACTAnimal cytoplasmic fatty acid synthase (FAS) represents a unique family of enzymes that are classically thought to be most closely related to fungal polyketide synthase (PKS). Recently, a widespread family of animal lipid metabolic enzymes has been described that bridges the gap between these two ubiquitous and important enzyme classes: the animal FAS-like PKSs (AFPKs). Although very similar in sequence to FAS enzymes that produce saturated lipids widely found in animals, AFPKs instead produce structurally diverse compounds that resemble bioactive polyketides. Little is known about the factors that bridge lipid and polyketide synthesis in the animals. Here, we describe the function of EcPKS2 from Elysia chlorotica, which synthesizes a complex polypropionate natural product found in this mollusc. EcPKS2 starter unit promiscuity potentially explains the high diversity of polyketides found in and among molluscan species. Biochemical comparison of EcPKS2 with the previously described EcPKS1 reveals molecular principles governing substrate selectivity that should apply to related enzymes encoded within the genomes of photosynthetic gastropods. Hybridization experiments combining EcPKS1 and EcPKS2 demonstrate the interactions between the ketoreductase and ketosynthase domains in governing the product outcomes. Overall, these findings enable an understanding of the molecular principles of structural diversity underlying the many molluscan polyketides likely produced by the diverse AFPK enzyme family.PMID:37695909 | DOI:10.1073/pnas.2305575120

Environ Sci Technol. 2023 Sep 11. doi: 10.1021/acs.est.3c03807. Online ahead of print.ABSTRACTInteractions and nutrient exchanges among members of microbial communities are important for understanding functional relationships in environmental microbiology. We can begin to elucidate the nature of these complex systems by taking a bottom-up approach utilizing simplified, but representative, community members. Here, we assess the effects of a toxic stress event, the addition of arsenite (As(III)), on a syntrophic co-culture containing lactate-fermenting Desulfovibrio vulgaris Hildenborough and solvent-dechlorinating Dehalococcoides mccartyi strain 195. Arsenic and trichloroethene (TCE) are two highly prevalent groundwater contaminants in the United States, and the presence of bioavailable arsenic is of particular concern at remediation sites in which reductive dechlorination has been employed. While we previously showed that low concentrations of arsenite (As(III)) inhibit the keystone TCE-reducing microorganism, D. mccartyi, this study reports the utilization of physiological analysis, transcriptomics, and metabolomics to assess the effects of arsenic on the metabolisms, gene expression, and nutrient exchanges in the described co-culture. It was found that the presence of D. vulgaris ameliorated arsenic stress on D. mccartyi, improving TCE dechlorination under arsenic-contaminated conditions. Nutrient and amino acid export by D. vulgaris may be a stress-ameliorating exchange in this syntrophic co-culture under arsenic stress, based on upregulation of transporters and increased extracellular nutrients like sarcosine and ornithine. These results broaden our knowledge of microbial community interactions and will support the further development and implementation of robust bioremediation strategies at multi-contaminant sites.PMID:37695749 | DOI:10.1021/acs.est.3c03807

Shock. 2023 Sep 5. doi: 10.1097/SHK.0000000000002220. Online ahead of print.ABSTRACTBACKGROUND: Trauma-induced hypocalcemia is common and associated with adverse outcomes, but the mechanisms remain unclear. Thus, we aimed to characterize the metabolomic and proteomic differences between normo- and hypocalcemic trauma patients to illuminate biochemical pathways that may underlie a distinct pathology linked with this clinical phenomenon.METHODS: Plasma was obtained on arrival from injured patients at a Level 1 Trauma Center. Samples obtained after transfusion were excluded. Multiple regression was used to adjust the omics data for injury severity and arrival base excess prior to metabolome- and proteome-wide comparisons between normo- (ionized Ca2+ > 1.0 mmol/L) and hypocalcemic (ionized Ca2+ ≤ 1.0 mmol/L) patients using partial least squares-discriminant analysis. OmicsNet and Gene Ontology were used for network and pathway analyses, respectively.RESULTS: Excluding isolated traumatic brain injury and penetrating injury, the main analysis included 36 patients (n = 14 hypocalcemic, n = 22 normocalcemic). Adjusted analyses demonstrated distinct metabolomic and proteomic signatures for normo- and hypocalcemic patients. Hypocalcemic patients had evidence of mitochondrial dysfunction (TCA cycle disruption, dysfunctional fatty acid oxidation), inflammatory dysregulation (elevated DAMPs, activated endothelial cells), aberrant coagulation pathways, and proteolytic imbalance with increased tissue destruction.CONCLUSIONS: Independent of injury severity, hemorrhagic shock, and transfusion, trauma-induced hypocalcemia is associated with early metabolomic and proteomic changes that may reflect unique pathology in hypocalcemic trauma patients. This study paves the way for future experiments to investigate mechanisms, identify intervenable pathways, and refine our management of hypocalcemia in severely injured patients.PMID:37695733 | DOI:10.1097/SHK.0000000000002220

Bioanalysis. 2023 Sep 11. doi: 10.4155/bio-2023-0131. Online ahead of print.ABSTRACTThis paper reviews the application of metabolomics in the early diagnosis of osteoporosis in recent years. The authors searched electronic databases for the keywords "metabolomics", "osteoporosis" and "biomarkers", then analyzed the relationship between functional markers and osteoporosis using categorical summarization. Lipid metabolism, amino acid metabolism and energy metabolism are closely related to osteoporosis development and can become early diagnostic markers of the condition. However, the existing studies in metabolomics suffer from varying application methods, difficulty in identifying isomers, small study cohorts and insufficient research on metabolic mechanisms. Consequently, it is important for future research to focus on broadening and standardizing the scope of the application of metabolomics. High-quality studies on a large scale should also be conducted while promoting the early diagnosis of osteoporosis in a more precise, comprehensive and sensitive manner.PMID:37695026 | DOI:10.4155/bio-2023-0131