Tryptophan Biosynthesis Research Articles

Transcriptome Analysis of Rice Embryo and Endosperm during Seed Germination.

Seed germination is a complex, multistage developmental process that is an important step in plant development. In this study, RNA-Seq was conducted in the embryo and endosperm of unshelled germinating rice seeds. A total of 14,391 differentially expressed genes (DEGs) were identified between the dry seeds and the germinating seeds. Of these DEGs, 7109 were identified in both the embryo and endosperm, 3953 were embryo specific, and 3329 were endosperm specific. The embryo-specific DEGs were enriched in the plant-hormone signal-transduction pathway, while the endosperm-specific DEGs were enriched in phenylalanine, tyrosine, and tryptophan biosynthesis. We categorized these DEGs into early-, intermediate-, and late-stage genes, as well as consistently responsive genes, which can be enriched in various pathways related to seed germination. Transcription-factor (TF) analysis showed that 643 TFs from 48 families were differentially expressed during seed germination. Moreover, 12 unfolded protein response (UPR) pathway genes were induced by seed germination, and the knockout of OsBiP2 resulted in reduced germination rates compared to the wild type. This study enhances our understanding of gene responses in the embryo and endosperm during seed germination and provides insight into the effects of UPR on seed germination in rice.

UPLC-QE-Orbitrap-Based Cell Metabolomics and Network Pharmacology to Reveal the Mechanism of N-Benzylhexadecanamide Isolated from Maca (Lepidium meyenii Walp.) against Testicular Dysfunction.

Testicular dysfunction (TDF) is characterized by testosterone deficiency and is caused by oxidative stress injury in Leydig cells. A natural fatty amide named N-benzylhexadecanamide (NBH), derived from cruciferous maca, has been shown to promote testosterone production. Our study aims to reveal the anti-TDF effect of NBH and explore its potential mechanism in vitro. This study examined the effects of H2O2 on cell viability and testosterone levels in mouse Leydig cells (TM3) under oxidative stress. In addition, cell metabolomics analysis based on UPLC-Q-Exactive-MS/MS showed that NBH was mainly involved in arginine biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, the TCA cycle and other metabolic pathways by affecting 23 differential metabolites, including arginine and phenylalanine. Furthermore, we also performed network pharmacological analysis to observe the key protein targets in NBH treatment. The results showed that its role was to up-regulate ALOX5, down-regulate CYP1A2, and play a role in promoting testicular activity by participating in the steroid hormone biosynthesis pathway. In summary, our study not only provides new insights into the biochemical mechanisms of natural compounds in the treatment of TDF, but also provides a research strategy that integrates cell metabolomics and network pharmacology in order to promote the screening of new drugs for the treatment of TDF.

Comparative Microscopic, Transcriptome and IAA Content Analyses Reveal the Stem Growth Variations in Two Cultivars Ilex verticillata.

Ilex verticillata is not only an excellent ornamental tree species for courtyards, but it is also a popular bonsai tree. 'Oosterwijk' and 'Red sprite' are two varieties of Ilex verticillata. The former has a long stem with few branches, while the latter has a short stem. In order to explain the stem growth differences between the two cultivars 'Oosterwijk' and 'Red sprite', determination of the microstructure, transcriptome sequence and IAA content was carried out. The results showed that the xylem thickness, vessel area and vessel number of 'Oosterwijk' were larger than in 'Red sprite'. In addition, our analysis revealed that the differentially expressed genes which were enriched in phenylpropanoid biosynthesis; phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis in the black and tan modules of the two varieties. We found that AST, HCT and bHLH 94 may be key genes in the formation of shoot difference. Moreover, we found that the IAA content and auxin-related DEGs GH3.6, GH3, ATRP5, IAA27, SAUR36-like, GH3.6-like and AIP 10A5-like may play important roles in the formation of shoot differences. In summary, these results indicated that stem growth variations of 'Oosterwijk' and 'Red sprite' were associated with DEGs related to phenylpropanoid biosynthesis, phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis, as well as auxin content and DEGs related to the auxin signaling pathway.

Altered adolescents obesity metabolism is associated with hypertension: a UPLC-MS-based untargeted metabolomics study.

This study aimed to explore the relationship between the plasma metabolites of adolescent obesity and hypertension and whether metabolite alterations had a mediating effort between adolescent obesity and hypertension. We applied untargeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to detect the plasma metabolomic profiles of 105 adolescents. All participants were selected randomly based on a previous cross-sectional study. An orthogonal partial least squares- discriminant analysis (OPLS-DA), followed by univariate statistics and enrichment analysis, was used to identify differential metabolites. Using logistic regression for variable selection, an obesity-related metabolite score (OMS, ) was constructed from the metabolites identified, and hypertension risk was estimated. In our study, based on P< 0.05, variable importance in projection (VIP) > 1.0, and impact value > 0.1, we identified a total of 12 differential metabolites. Significantly altered metabolic pathways were the sphingolipid metabolism, purine metabolism, pyrimidine metabolism, phospholipid metabolism, steroid hormone biosynthesis, tryptophan, tyrosine, and phenylalanine biosynthesis. The logistic regression selection resulted in a four-metabolite score (thymidine, sphingomyelin (SM) d40:1, 4-hydroxyestradiol, and L-lysinamide), which was positively associated with hypertension risk (odds ratio: 7.79; 95% confidence interval: 2.13, 28.47; for the quintile 4 compared with quartile 1 of OMS) after multivariable adjustment. The OMS constructed from four differential metabolites was used to predict the risk of hypertension in adolescents. These findings could provide sensitive biomarkers for the early recognition of hypertension in adolescents with obesity.

Metabolome Profiling and Pathway Analysis in Metabolically Healthy and Unhealthy Obesity among Chinese Adolescents Aged 11-18 Years.

The underlying mechanisms of the development of unhealthy metabolic phenotypes in obese children and adolescents remain unclear. We aimed to screen the metabolomes of individuals with the unhealthy obesity phenotype and identify the potential metabolic pathways that could regulate various metabolic profiles of obesity in Chinese adolescents. A total of 127 adolescents aged 11-18 years old from China were investigated using a cross-sectional study. The participants were classified as having metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO) based on the presence/absence of metabolic abnormalities defined by metabolic syndrome (MetS) and body mass index (BMI). Serum-based metabolomic profiling using gas chromatography-mass spectrometry (GC-MS) was undertaken on 67 MHO and 60 MUO individuals. ROC analyses showed that palmitic acid, stearic acid, and phosphate could predict MUO, and that glycolic acid, alanine, 3-hydroxypropionic acid, and 2-hydroxypentanoic acid could predict MHO (all p < 0.05) from selected samples. Five metabolites predicted MUO, 12 metabolites predicted MHO in boys, and only two metabolites predicted MUO in girls. Moreover, several metabolic pathways may be relevant in distinguishing the MHO and MUO groups, including the fatty acid biosynthesis, fatty acid elongation in mitochondria, propanoate metabolism, glyoxylate and dicarboxylate metabolism, and fatty acid metabolism pathways. Similar results were observed for boys except for phenylalanine, tyrosine and tryptophan biosynthesis, which had a high impact [0.098]. The identified metabolites and pathways could be efficacious for investigating the underlying mechanisms of the development of different metabolic phenotypes in obese Chinese adolescents.

Metabolomics profile and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score.

The intermediate metabolites associated with the development of atherosclerotic cardiovascular disease (ASCVD) remain largely unknown. Thus, we conducted a large panel of metabolomics profiling to identify the new candidate metabolites that were associated with 10-year ASCVD risk. Thirty acylcarnitines and twenty amino acids were measured in the fasting plasma of 1,102 randomly selected individuals using a targeted FIA-MS/MS approach. The 10-year ASCVD risk score was calculated based on 2013 ACC/AHA guidelines. Accordingly, the subjects were stratified into four groups: low-risk (n = 620), borderline-risk (n = 110), intermediate-risk (n = 225), and high-risk (n = 147). 10 factors comprising collinear metabolites were extracted from principal component analysis. C4DC, C8:1, C16OH, citrulline, histidine, alanine, threonine, glycine, glutamine, tryptophan, phenylalanine, glutamic acid, arginine, and aspartic acid were significantly associated with the 10-year ASCVD risk score (p-values ≤ 0.044). The high-risk group had higher odds of factor 1 (12 long-chain acylcarnitines, OR = 1.103), factor 2 (5 medium-chain acylcarnitines, OR = 1.063), factor 3 (methionine, leucine, valine, tryptophan, tyrosine, phenylalanine, OR = 1.074), factor 5 (6 short-chain acylcarnitines, OR = 1.205), factor 6 (5 short-chain acylcarnitines, OR = 1.229), factor 7 (alanine, proline, OR = 1.343), factor 8 (C18:2OH, glutamic acid, aspartic acid, OR = 1.188), and factor 10 (ornithine, citrulline, OR = 1.570) compared to the low-risk ones; the odds of factor 9 (glycine, serine, threonine, OR = 0.741), however, were lower in the high-risk group. "D-glutamine and D-glutamate metabolism", "phenylalanine, tyrosine, and tryptophan biosynthesis", and "valine, leucine, and isoleucine biosynthesis" were metabolic pathways having the highest association with borderline/intermediate/high ASCVD events, respectively. Abundant metabolites were found to be associated with ASCVD events in this study. Utilization of this metabolic panel could be a promising strategy for early detection and prevention of ASCVD events.

Yi-Shen-Hua-Shi granule ameliorates diabetic kidney disease by the "gut-kidney axis".

Yi-Shen-Hua-Shi (YSHS) granule is an effective prescription widely used in traditional Chinese medicine to treat diabetic kidney disease (DKD), its exact efficacy in treating DKD has been confirmed but the underlying regulatory mechanism has not been fully elucidated. To explore the mechanism by which YSHS granule regulates intestinal flora and serum metabolites and then regulates renal mRNA expression through the "gut-kidney axis", so as to improve DKD. 40 rats were divided into five groups: Normal group (N) (normal saline), model group (M) (STZ+normal saline), YSHS granule low-dose group (YL) (STZ+2.27g kg-1 d-1), YSHS granule high-dose group (YH) (STZ+5.54g kg-1 d-1) and valsartan group (V) (STZ+7.38mg kg-1 d-1). After 6 weeks, changes in blood glucose, blood lipids, and renal function related indexes were observed, as well as pathological changes in the kidney and colon. Intestinal microbiota was sequenced by 16S rDNA, serum differential metabolites were identified by LC-MS/MS, and renal differences in mRNA expression were observed by RNA-seq. Further, through the association analysis of intestinal differential microbiota, serum differential metabolites and kidney differential mRNAs, the target flora, target metabolites and target genes of YSHS granule were screened and verified, and the "gut-metabolism-transcription" co-expression network was constructed. In group M, blood glucose, blood lipid and proteinuria were increased, inflammation, oxidative stress and renal function were aggravated, with the proliferation of mesangial matrix, vacuolar degeneration of renal tubules, accumulation of collagen and lipid, and increased intestinal permeability, and YSHS granule and valsartan improved these disorders to varying degrees. High dose of YSHS granule improved the diversity and abundance of flora, decreased the F/B value, greatly increased the abundance of Lactobacillus and Lactobacillus_murinus, and decreased the abundance of Prevoella UCG_001. 14 target metabolites of YSHS granule were identified, which were mainly enriched in 20 KEGG pathways, such as Glycerophospholipid metabolism, Sphingolipid metabolism and Phenylalanine, tyrosine and tryptophan biosynthesis. 96 target mRNAs of YSHS granule were also identified. The enriched top 20 pathways were closely related to glucose and lipid metabolism, of which a total of 21 differential mRNAs were expressed. Further correlation analysis revealed that Lactobacillus, Lactobacillus_murinus and Prevotella UCG_001 were highly correlated with Glycerophospholipid metabolism, Sphingolipid metabolism and Phenylalanine, tyrosine and tryptophan biosynthesis pathways. At the same time, 6 pathways including Glycerophospholipid metabolism, Arachidonic acid metabolism, Purine metabolism, Primary bile acid biosynthesis, Ascorbate and aldarate metabolism and Galactose metabolism were co-enriched by the target metabolites and the target mRNAs of YSHS granule, including 7 differential metabolites such as phosphatidylethanolamine and 7 differential genes such as Adcy3. The 7 differential metabolites had high predictive value of AUC, and the validation of 7 differential genes were highly consistent with the sequencing results. YSHS granule could improve DKD through the "gut-kidney axis". Lactobacillus and Lactobacillus_murinus were the main driving forces. 6 pathways related to glucose and lipid metabolism, especially Glycerophospholipid metabolism, may be an important follow-up response and regulatory mechanism.

Metabolomics study of Berberidis Radix in intervening ulcerative colitis based on UPLC-Q-TOF-MS

The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.

Analysis of Plasma Metabolomics of Liver Fibrosis Based on Bioinformatics

Objective: To explore the metabolites of liver fibrosis and their interactions based on bibliometrics, and to find biomarkers and therapeutic targets for liver fibrosis. Methods: Combined Chinese and English databases were used to collect plasma metabolomics studies of liver fibrosis. Recurring metabolites from the included studies were collected as liver fibrosis metabolite profiles, and metabolites were analyzed and processed on metabolism-related databases. Results: A total of 16 articles were included, and 24 recurring metabolites were selected as the metabolite spectrum of liver fibrosis, and they appeared in 24 metabolic pathways. Topological analysis of the pathways on the MetPA database revealed that aminyl tRNA synthesis, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, sphingolipid metabolism, phenylalanine metabolism, arginine and proline metabolism, bile acid biosynthesis, and glycolytic/glycoisogenic metabolic pathways were associated with liver fibrosis. Valine, arginine and leucine occur more than 5 times. Conclusion: The pathological mechanism of liver fibrosis involves the biological metabolism of amino acids, proteins, lipids, carbohydrates, and bile acids. Valine, arginine and leucine can be used as biomarkersof liver fibrosis.

Effect of Lactobacillus Rhamnosus GG for Regulation of Inflammatory Response in Radiation-Induced Enteritis.

The purpose of this study was to investigate the role of Lactobacillus rhamnosus GG (LGG) probiotics in radiation enteritis using in vivo mice. A total of 40 mice were randomly assigned to four groups: control, probiotics, radiotherapy (RT), and RT + probiotics. For the group of probiotics, 0.2mL of solution that contained 1.0 × 108 colony-forming units (CFU) of LGG was used and orally administered daily until sacrifice. For RT, a single dose of 14Gy was administered using a 6 mega-voltage photon beam to the abdominopelvic area. Mice were sacrifice at day 4 (S1) and day 7 (S2) after RT. Their jejunum, colon, and stool were collected. A multiplex cytokine assay and 16s ribosomal RNA amplicon sequencing were then performed. Regarding cytokine concentrations in tissues, pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 and monocyte chemotactic protein-1, showed significantly decreased protein levels in colon tissues of the RT + probiotics group than in the RT alone group (all p < 0.05). As for comparing microbial abundance through alpha-diversity and beta-diversity, no significant differences were observed between the RT + probiotics and RT alone groups, except for an increase in alpha-diversity in the stool of the RT + probiotics group. Upon analysis of differential microbes based on treatment, the dominance of anti-inflammatory-related microbes, such as Porphyromonadaceae, Bacteroides acidifaciens, and Ruminococcus, was observed in the jejunum, colon, and stool of the RT + probiotics group. With regard to predicted metabolic pathway abundances, the pathways associated with anti-inflammatory processes, such as biosynthesis of pyrimidine nucleotides, peptidoglycans, tryptophan, adenosylcobalamin, and propionate, were differentially identified in the RT + probiotics group compared to the RT alone group. Protective effects of probiotics on radiation enteritis were potentially derived from dominant anti-inflammation-related microbes and metabolites.

Metabolic signature of Mycobacterium avium subsp. paratuberculosis infected and infectious dairy cattle by integrating nuclear magnetic resonance analysis and blood indices.

The early diagnosis of Mycobacterium avium subsp. paratuberculosis (MAP) is one of the current challenges of farmers and veterinarians. This work aimed to investigate the changes in metabolic levels associated with natural MAP infection in infected and infectious dairy cattle. The study included sera from 23 infectious/seropositive, 10 infected but non-infectious/seronegative, and 26 negative Holstein Fresian cattle. The samples were selected from a collection of samples gathered during a prospective study. The samples were analyzed by quantitative nuclear magnetic resonance (NMR) spectroscopy and routine blood chemistry. The blood indices and the 1H NMR data were concatenated by low-level data fusion, resulting in a unique global fingerprint. Afterwards, the merged dataset was statistically analyzed by the least absolute shrinkage and selection operator (LASSO), which is a shrinkage and selection method for supervised learning. Finally, pathways analysis was performed to get more insights on the possible dysregulated metabolic pathways. The LASSO model achieved, in a 10 time repeated 5-fold cross-validation, an overall accuracy of 91.5% with high values of sensitivity and specificity in classifying correctly the negative, infected, and infectious animals. The pathway analysis revealed MAP-infected cattle have increased tyrosine metabolism and enhanced phenylalanine, tyrosine and tryptophan biosynthesis. The enhanced synthesis and degradation of ketone bodies was observed both in infected and infectious cattle. In conclusion, fusing data from multiple sources has proved to be useful in exploring the altered metabolic pathways in MAP infection and potentially diagnosing negative animals within paratuberculosis-infected herds.

The activities and mechanisms of intestinal microbiota metabolites of TCM herbal ingredients could be illustrated by a strategy integrating spectrum-effects, network pharmacology, metabolomics and molecular docking analysis: Platycodin D as an example

BackgroundThe intestinal microbiota plays a key role in understanding the mechanism of traditional Chinese medicine (TCM), as it could transform the herbal ingredients to metabolites with higher bioavailability and activity comparing to their prototypes. Nevertheless, the study of the activity and mechanism of microbiota metabolites reported by the published literature still lacks viable ways. Hence a new strategy is proposed to solve this issue. PurposeA new strategy to study the activity and mechanism of intestinal microbiota metabolites of TCM herbal ingredients by integrating spectrum-effect relationship, network pharmacology, metabolomics analysis and molecular docking together was developed and proposed. MethodPlatycodin D (PD) and its microbiota metabolites with antitussive and expectorant effect were selected as an example for demonstration. First, the PD and its microbiota metabolites with important contribution to antitussive and/or expectorant effects were screened through spectrum-effect relationship analysis. Second, network pharmacology and metabolomics analysis were integrated to identify the upstream key targets of PD and its microbiota metabolites as well as the downstream endogenous metabolites. Finally, the active forms of PD were further confirmed by molecular docking. ResultsResults showed that PD was an active ingredient with antitussive and/or expectorant effects, and the active forms of PD were its microbiota metabolites: 3-O-β-d-glucopyranosyl platycodigenin, 3-O-β-d-glucopyranosyl isoplatycodigenin, 7‑hydroxyl-3-O-β-d-glucopyranosyl platycodigenin, platycodigenin and isoplatycodigenin. In addition, those microbiota metabolites could bind the key targets of PAH, PLA2G2A, ALOX5, CYP2C9 and CYP2D6 to exert antitussive effects by regulating four metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Similarly, they could also bind the key targets of PLA2G1B, ALOX5, CYP2C9 and CYP2D6 to exert expectorant effect by regulating two pathways of glycerophospholipid metabolism and linoleic acid metabolism. ConclusionThe proposed strategy paves a new way for the illustration of the activities and mechanisms of TCM herbal ingredients, which is very important to reconcile the conundrums of TCM herbal ingredients with low oral bioavailability but high activity.

Metagenomic and Untargeted Metabolomic Analysis of the Effect of Sporisorium reilianum Polysaccharide on Improving Obesity.

Gut microbiota plays an important role in the pathophysiology of obesity. Fungal polysaccharide can improve obesity, but the potential mechanism needs further study. This experiment studied the potential mechanism of polysaccharides from Sporisorium reilianum (SRP) to improve obesity in male Sprague Dawley (SD) rats fed with a high-fat diet (HFD) using metagenomics and untargeted metabolomics. After 8 weeks of SRP (100, 200, and 400 mg/kg/day) intervention, we analyzed the related index of obesity, gut microbiota, and untargeted metabolomics of rats. The obesity and serum lipid levels of rats treated with SRP were reduced, and lipid accumulation in the liver and adipocyte hypertrophy was improved, especially in rats treated with a high dose of SRP. SRP improved the composition and function of gut microbiota in rats fed with a high-fat diet, and decreased the ratio of Firmicutes to Bacteroides at the phylum level. At the genus level, the abundance of Lactobacillus increased and that of Bacteroides decreased. At the species level, the abundance of Lactobacillus crispatus, Lactobacillus helveticus, and Lactobacillus acidophilus increased, while the abundance of Lactobacillus reuteri and Staphylococcus xylosus decreased. The function of gut microbiota mainly regulated lipid metabolism and amino acid metabolism. The untargeted metabolomics indicated that 36 metabolites were related to the anti-obesity effect of SRP. Furthermore, linoleic acid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and the phenylalanine metabolism pathway played a role in improving obesity in those treated with SRP. The study results suggest that SRP significantly alleviated obesity via gut-microbiota-related metabolic pathways, and SRP could be used for the prevention and treatment of obesity.

Fecal Metabolomics Reveals the Foraging Strategies of Giant Pandas for Different Parts of Bamboo.

Climate change-induced food shortages pose major threats to wildlife conservation, and the exclusive reliance of giant pandas on bamboo makes them particularly vulnerable. The aim of this study was to provide insight into the reasons for the foraging strategies of giant pandas to selectively forage for different bamboo parts (bamboo shoot, culm, and leaf) during different seasons. This study used a metabolomic approach to analyze the fecal metabolites of giant pandas and conducted a correlation analysis with their gut microbiota. The results indicate that the fecal metabolites of giant pandas differ significantly depending on the bamboo parts they forage on, with higher sugar content observed when they consume bamboo culm with high fiber content. By functional annotation, culm group metabolites were enriched in the galactose metabolic pathway, while shoot group metabolites were enriched in the phenylalanine, tyrosine and tryptophan biosynthesis pathways. Moreover, Streptococcus showed a significant positive correlation with glucose and acetic acid content. Therefore, the foraging strategy of giant pandas is based on the ability to utilize the nutrient content of different bamboo parts. Captive feeding and habitat construction should enrich bamboo species to allow them to express their natural foraging strategies and improve their welfare and reproductive status.

Draft Genome Sequence of Pseudomonas carnis Strain 23-145, Causing Blue Discolorations on Rabbit Carcasses.

Here, we report the genome sequence of Pseudomonas carnis strain 23-145, which was recovered from a rabbit carcass with blue discolorations. The strain harbored two trpABCDF loci involved in tryptophan biosynthesis, which is characteristic of blue-pigment-producing Pseudomonas strains.

Phosphorus and Serendipita indica synergism augments arsenic stress tolerance in rice by regulating secondary metabolism related enzymatic activity and root metabolic patterns

The multifarious problems created by arsenic (As), for collective environment and human health, serve a cogent case for searching integrative agricultural approaches to attain food security. Rice (Oryza sativa L.) acts as a sponge for heavy metal(loid)s accretion, specifically As, due to anaerobic flooded growth conditions facilitating its uptake. Acclaimed for their positive impact on plant growth, development and phosphorus (P) nutrition, ‘mycorrhizas’ are able to promote stress tolerance. Albeit, the metabolic alterations underlying Serendipita indica (S. indica; S.i) symbiosis-mediated amelioration of As stress along with nutritional management of P are still understudied. By using biochemical, RT-qPCR and LC-MS/MS based untargeted metabolomics approach, rice roots of ZZY-1 and GD-6 colonized by S. indica, which were later treated with As (10 µM) and P (50 µM), were compared with non-colonized roots under the same treatments with a set of control plants. The responses of secondary metabolism related enzymes, especially polyphenol oxidase (PPO) activities in the foliage of ZZY-1 and GD-6 were enhanced 8.5 and 12-fold, respectively, compared to their respective control counterparts. The current study identified 360 cationic and 287 anionic metabolites in rice roots, and the commonly enriched pathway annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was biosynthesis of phenylalanine, tyrosine and tryptophan, which validated the results of biochemical and gene expression analyses associated with secondary metabolic enzymes. Particularly under As+S.i+P comparison, both genotypes exhibited an upregulation of key detoxification and defense related metabolites, including fumaric acid, L-malic acid, choline, 3,4-dihydroxybenzoic acid, to name a few. The results of this study provided the novel insights into the promising role of exogenous P and S. indica in alleviating As stress.

Structural characterization of a fucoidan from Ascophyllum nodosum and comparison of its protective effect against cellular oxidative stress with its analogues

In the present study, a fucoidan fraction (ANP-3) was isolated from Ascophyllum nodosum, and the combined application of desulfation, methylation, HPGPC, HPLC-MSn, FT-IR, GC–MS, NMR, and Congo red test elucidated ANP-3 (124.5 kDa) as a triple-helical sulfated polysaccharide constituted by →2)-α-Fucp3S-(1→, →3)-α-Fucp2S4S-(1→, →3,6)-β-Galp4S-(1→, →3,6)-β-Manp4S-(1→, →3,6)-β-Galp4S-(1→，→6)-β-Manp-(1→, →3)-β-Galp-(1→, α-Fucp-(1→, and α-GlcAp-(1→ residues. To better understand the relationship between the fucoidan structure of A. nodosum and protective effects against oxidative stress, two fractions ANP-6 and ANP-7 were used as contrast. ANP-6 (63.2 kDa) exhibited no protective effect against H2O2-induced oxidative stress. However, ANP-3 and ANP-7 with the same molecular weight of 124.5 kDa could protect against oxidative stress by down-regulating reactive oxygen species (ROS) and malondialdehyde (MDA) levels and up-regulating total antioxidant capability (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities. Then metabolites analysis indicated that arginine biosynthesis and phenylalanine, tyrosine, and tryptophan biosynthesis metabolic pathways and metabolic biomarkers such as betaine were involved in the effects of ANP-3 and ANP-7. The better protective effect of ANP-7 compared to that of ANP-3 could be attributed to its relatively higher molecular weight, sulfate substitution and →6)-β-Galp-(1→ content, and lower uronic acid content.

NMR-Based Metabolomics to Analyze the Effects of a Series of Monoamine Oxidases-B Inhibitors on U251 Cells.

Alzheimer's disease (AD) is a typical progressive neurodegenerative disorder, and with multiple possible pathogenesis. Among them, coumarin derivatives could be used as potential drugs as monoamine oxidase-B (MAO-B) inhibitors. Our lab has designed and synthesized coumarin derivatives based on MAO-B. In this study, we used nuclear magnetic resonance (NMR)-based metabolomics to accelerate the pharmacodynamic evaluation of candidate drugs for coumarin derivative research and development. We detailed alterations in the metabolic profiles of nerve cells with various coumarin derivatives. In total, we identified 58 metabolites and calculated their relative concentrations in U251 cells. In the meantime, the outcomes of multivariate statistical analysis showed that when twelve coumarin compounds were treated with U251cells, the metabolic phenotypes were distinct. In the treatment of different coumarin derivatives, there several metabolic pathways changed, including aminoacyl-tRNA biosynthesis, D-glutamine and D-glutamate metabolism, glycine, serine and threonine metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glutathione metabolism and valine, leucine and isoleucine biosynthesis. Our work documented how our coumarin derivatives affected the metabolic phenotype of nerve cells in vitro. We believe that these NMR-based metabolomics might accelerate the process of drug research in vitro and in vivo.

Untargeted metabolomics analysis of cerebrospinal fluid in patients with leptomeningeal metastases from non-small cell lung cancer

ABSTRACT Objective: To explore and analyze the diagnostic value of metabolic markers in cerebrospinal fluid (CSF) in leptomeningeal metastases (LM) of non-small cell lung cancer (NSCLC). Methods: Forty-six CSF samples from patients with NSCLC-LM were collected. Another 48 CSF samples from patients with nonmalignant neurological diseases were selected as control group. Metabolomic analysis of CSF was performed by high-performance liquid chromatography-mass spectrometry. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied for modeling. A multi-criteria evaluation system (variable importance value >1, multiple of change >2 and P < 0.05 for univariate analysis) was used to find differential metabolites between two groups. The subject working characteristic curves and pathway enrichment analysis were used to screen metabolites and pathways associated with NSCLC-LM. Results: The PCA model and OPLS-DA model showed good overall data quality. Thirty endogenous differential metabolites were screened, and six potential biomarkers were further identified, including tyrosine (t = 3.37, P = 0.024, AUC = 0.967), phenylalanine (t = 3.98, P < 0.001, AUC = 0.992), pyruvate (t = 4.48, P < 0.001, AUC = 0.976), tryptophan (t = −2.5, P = 0.014, AUC = 0.935), adenosine monophosphate (t = −6.13, P < 0.001, AUC = 0.932) and glucose (t = −4.00, P < 0.001, AUC = 0.993). Thirty differential metabolites screened were subjected to metabolic pathway enrichment analysis and matched to 20 relevant metabolic pathways, of which the four most likely to cause metabolite changes were as follows: glycolysis and sugar metabolism synthesis, pyruvate metabolism, phenylalanine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis. Conclusions: Untargeted metabolomics can effectively screen for CSF metabolites specific to NSCLC-LM patients, and six potential metabolites and their metabolic pathways might be involved in the pathogenesis of NSCLC-LM.

Expanding the application of tryptophan: Industrial biomanufacturing of tryptophan derivatives.

Tryptophan derivatives are various aromatic compounds produced in the tryptophan metabolic pathway, such as 5-hydroxytryptophan, 5-hydroxytryptamine, melatonin, 7-chloro-tryptophan, 7-bromo-tryptophan, indigo, indirubin, indole-3-acetic acid, violamycin, and dexoyviolacein. They have high added value, widely used in chemical, food, polymer and pharmaceutical industry and play an important role in treating diseases and improving life. At present, most tryptophan derivatives are synthesized by biosynthesis. The biosynthesis method is to combine metabolic engineering with synthetic biology and system biology, and use the tryptophan biosynthesis pathway of Escherichia coli, Corynebacterium glutamicum and other related microorganisms to reconstruct the artificial biosynthesis pathway, and then produce various tryptophan derivatives. In this paper, the characteristics, applications and specific biosynthetic pathways and methods of these derivatives were reviewed, and some strategies to increase the yield of derivatives and reduce the production cost on the basis of biosynthesis were introduced in order to make some contributions to the development of tryptophan derivatives biosynthesis industry.