PubMed

Leaf metabolic signatures induced by real and simulated herbivory in black mustard (Brassica nigra). Metabolomics. 2019 Sep 28;15(10):130 Authors: Papazian S, Girdwood T, Wessels BA, Poelman EH, Dicke M, Moritz T, Albrectsen BR Abstract INTRODUCTION: The oxylipin methyl jasmonate (MeJA) is a plant hormone active in response signalling and defence against herbivores. Although MeJA is applied experimentally to mimic herbivory and induce plant defences, its downstream effects on the plant metabolome are largely uncharacterized, especially in the context of primary growth and tissue-specificity of the response. OBJECTIVES: We investigated the effects of MeJA-simulated and real caterpillar herbivory on the foliar metabolome of the wild plant Brassica nigra and monitored the herbivore-induced responses in relation to leaf ontogeny. METHODS: As single or multiple herbivory treatments, MeJA- and mock-sprayed plants were consecutively exposed to caterpillars or left untreated. Gas chromatography (GC) and liquid chromatography (LC) time-of-flight mass-spectrometry (TOF-MS) were combined to analyse foliar compounds, including central primary and specialized defensive plant metabolites. RESULTS: Plant responses were stronger in young leaves, which simultaneously induced higher chlorophyll levels. Both MeJA and caterpillar herbivory induced similar, but not identical, accumulation of tricarboxylic acids (TCAs), glucosinolates (GSLs) and phenylpropanoids (PPs), but only caterpillar feeding led to depletion of amino acids. MeJA followed by caterpillars caused higher induction of defence compounds, including a three-fold increase in the major defence compound allyl-GSL (sinigrin). When feeding on MeJA-treated plants, caterpillars gained less weight indicative of the reduced host-plant quality and enhanced resistance. CONCLUSIONS: The metabolomics approach showed that plant responses induced by herbivory extend beyond the regulation of defence metabolism and are tightly modulated throughout leaf development. This leads to a new understanding of the plant metabolic potential that can be exploited for future plant protection strategies. PMID: 31563978 [PubMed - in process]

Proteobacteria Acts as a Pathogenic Risk-Factor for Chronic Abdominal Pain and Diarrhea in Post-Cholecystectomy Syndrome Patients: A Gut Microbiome Metabolomics Study. Med Sci Monit. 2019 Sep 29;25:7312-7320 Authors: Kang Z, Lu M, Jiang M, Zhou D, Huang H Abstract BACKGROUND Laparoscopic cholecystectomy (LC) is regarded as the criterion standard for gallstone therapy, but post-cholecystectomy syndrome (PCS) is a common complication. This study aimed to analyze and identify differences in gut microbiome in PCS patients. MATERIAL AND METHODS This study involved 8 PCS patients (RS1), 8 asymptomatic PCS patients (RS2), and 8 healthy individuals (RS3). Genomic DNA of gut microbiome was extracted and amplified with CTAB method. PCR products were sequenced with Illumina High-Through Sequencing. Sequencing data were analyzed with QIIME software. Effective sequence of bacterial 16S-rRNA gene was clustered into OTUs using UPARSE software. Species annotations were evaluated using Mothur software. QIIME software was used to conduct complexity analysis and calculate UniFrac distances. R software was used to generate PCoA plots. RESULTS Bacterial 16S-rDNA gene sequences showed that the effective species annotative data were more than 97%. According to Ternary plot, Firmicutes and Bacteroidetes had similar abundance and contents among the 3 groups. Contents of Proteobacteria in RS1 were higher compared to RS2 and RS3. Bacterial genomic DNAs samples were clustered together in the same group; however, distances were relative far between different groups. RS1 illustrated significantly higher abundance of Proteobacteria colonies compared to healthy people (p<0.05), and illustrated higher abundance of Verrucomicrobia and lower abundance of Bacteroidetes and Firmicutes, but without significant differences (p>0.05). CONCLUSIONS Gut microbiome of PCS patients was dominated by Proteobacteria in feces and contained little Firmicutes and Bacteroidetes. The enhanced abundance of Proteobacteria might be the highly pathogenic risk factor for chronic abdominal pain and diarrhea in PCS patients. PMID: 31563920 [PubMed - in process]

Comprehensive metabolic profiles of seminal plasma with different forms of male infertility and their correlation with sperm parameters. J Pharm Biomed Anal. 2019 Sep 21;177:112888 Authors: Xu Y, Lu H, Wang Y, Zhang Z, Wu Q Abstract Metabolomics measurements of seminal plasma are widely used in diagnosis and finding of molecular mechanisms of male infertility. However, so far the limitation of metabolome coverage of analytical methods hinders comprehensive metabolite biomarker finding. Moreover, the widely used case-control comparison is not enough to unveil the detailed correlations of the metabolic changes with different sperm abnormalities. In this work, we aimed to have comprehensive metabolic profiling of seminal plasma to find the metabolomics difference between healthy controls and infertility case samples with different semen abnormities by liquid chromatography-mass spectrometry (LC-MS) detection with previously established new sample preparation procedure. Among 624 detected metabolite features, 63 potential biomarkers in various metabolite classes were found for infertility in seminal plasma by multivariate analysis. Interestingly, different infertility forms have different potential biomarkers with few in common, and most of potential biomarkers were found in oligo-astheno-teratospermia samples. To further find the association of the metabolomic changes with specific sperm abnormality, sperm parameters including sperm concentration, sperm deformity rate and sperm motility were also collected, and multivariate linear regression was used to find correlations between sperm parameters and potential biomarkers. Finally, levels of 17 metabolites were found to be significantly correlated with sperm parameters. Most of correlations agreed with previously reported mechanisms of infertility, such as correlation of acylcarnitines with sperm concentration and sperm deformity, and correlation of some antioxidants with sperm deformity rate and sperm motility. Some correlations were reported for the first time, such as negative correlations of isopentenyl pyrophosphate, 2-phosphoglyceric acid and γ-glutamyl-Se-methylselenocysteine with sperm deformity rate, and negative correlation of creatine riboside with sperm concentration. All the potential biomarkers were involved in 14 metabolic pathways playing important role in energy production, antioxidation, hormone regulation and sperm membrane. These results proved previously reported molecular mechanism (such as oxidative stress and energy production) and also gave new possible clues to the pathology of male infertility, which will benefit future etiology, diagnosis and treatment of male infertility. PMID: 31563758 [PubMed - as supplied by publisher]

The influence of polyphenols on metabolic disorders caused by compounds released from plastics - Review. Chemosphere. 2019 Sep 20;240:124901 Authors: Żwierełło W, Maruszewska A, Skórka-Majewicz M, Goschorska M, Baranowska-Bosiacka I, Dec K, Styburski D, Nowakowska A, Gutowska I Abstract Persistent organic pollutants (POPs) released from plastics into water, soil and air are significant environmental and health problem. Continuous exposure of humans to these substances results not only from the slow biodegradation of plastics but also from their ubiquitous use as industrial materials and everyday products. Exposure to POPs may lead to neurodegenerative disorders, induce inflammation, hepatotoxicity, nephrotoxicity, insulin resistance, allergies, metabolic diseases, and carcinogenesis. This has spurred an increasing intense search for natural compounds with protective effects against the harmful components of plastics. In this paper, we discuss the current state of knowledge concerning the protective functions of polyphenols against the toxic effects of POPs: acrylonitrile, polychlorinated biphenyls, dioxins, phthalates and bisphenol A. We review in detail papers from the last two decades, analyzing POPs in terms of their sources of exposure and demonstrate how polyphenols may be used to counteract the harmful environmental effects of POPs. The protective effect of polyphenols results from their impact on the level and activity of the components of the antioxidant system, enzymes involved in the elimination of xenobiotics, and as a consequence - on the level of reactive oxygen species (ROS). Polyphenols present in daily diet may play a protective role against the harmful effects of POPs derived from plastics, and this interaction is related, among others, to the antioxidant properties of these compounds. To our knowledge, this is the first extensive review of in vitro and in vivo studies concerning the molecular mechanisms of interactions between selected environmental toxins and polyphenols. PMID: 31563713 [PubMed - as supplied by publisher]

The study of neuroprotective effect of ferulic acid based on cell metabolomics. Eur J Pharmacol. 2019 Sep 26;:172694 Authors: Yin CL, Lu RG, Zhu JF, Zhu HJ, Liu X, Li QF, Mo YY, Huang HM, Chin B, Wu JX, Liu XW, Cheng B, Ruan JX, Liang YH, Song H, Zheng H, Guo HW, Su ZH Abstract Ferulic acid (FA), a naturally derived phenolic compound, has antioxidant and antidepressant-like effects. It is still a challenge to study its mechanism due to the complexity of the pathophysiology of depression. In this study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to perform metabolomics studies based on biochemical changes in differentiated rat pheochromocytoma (PC12) cells treated with corticosterone-induced neurological damage after FA treatment. A total of 31 metabolites were identified as potential biomarkers for corticosterone-induced PC12 cells injury. Among them, 24 metabolites were regulated after FA treatment. Pathway analysis revealed that these metabolites were mainly involved in the amino acid metabolism, energy metabolism and glycerophospholipid metabolism. In addition, based on the results of metabolomics, three cell signaling pathways related to glutamate were discovered. To further study the interactions between FA and major targets in three signaling pathways, a molecular docking method was employed. The results showed that FA had the strongest binding power with protein kinase B (AKT). Furthermore, the result of mRNA changes analyzed by quantitative real time RT-PCR indicated that AKT and protein kinase A (PKA) in the signaling pathway were up regulated after treatment with FA compared with model group. This study shows that strategies based on cell metabolomics associated with molecular docking and molecular biology is a helpful tool to elucidate the neuroprotective mechanism of FA. PMID: 31563648 [PubMed - as supplied by publisher]

Comparative study of five different amine-derivatization methods for metabolite analyses by liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2019 Sep 10;:460536 Authors: Lkhagva A, Shen CC, Leung YS, Tai HC Abstract Current metabolomics research utilizes liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses to handle biological samples that contain thousands of quantifiable metabolites. However, no LC-MS/MS condition is suitable for directly analyzing all metabolites. An alternative approach is to derivatize metabolites to impart desirable properties such as better chromatographic separation, enhanced ionization efficiency, or fluorescence detection. An important category of metabolites is amine-containing compounds, which includes amino acids, neurotransmitters, alkaloids, biogenic amines, etc. Various derivatization methods have been developed for amine groups, but few studies have compared their relative strengths and weaknesses. We chose Dansyl-Cl, o-phthalaldehyde (OPA), Fmoc-Cl, Dabsyl-Cl, and Marfey's reagent to systematically compare their reactivity, absorbance, fluorescence, chromatographic separation, and ionization efficiencies under three pH conditions-2.6, 5.0, and 8.0. Their MS/MS fragmentation patterns were also examined under different collision energies. Overall, Dansyl-Cl is a very versatile derivatization method, generating products with fluorescence and high ionization efficiency. Fmoc-Cl is similarly useful under highly acidic chromatography conditions. Dabsyl-Cl may be a good alternative at weakly acidic and weakly basic conditions. OPA is a versatile fluorogenic reagent and its chemistry may be fine-tuned by incorporating different thiol molecules. Marfey's reagent is suboptimal in general, but its chiral property is useful for the separation of enantiomers. All five were applied to the analyses of Coptis chinensis, a Chinese medical herb, identifying hundreds of amine-containing metabolites through MS/MS analyses. None of the five methods is clearly superior, and their compound coverage profiles are rather distinct. A combination of multiple derivatization reagents is required for comprehensive coverage. Our comparative data provide useful guidelines for designing more efficient metabolomics experiments for different analytical goals. PMID: 31563299 [PubMed - as supplied by publisher]

35 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/09/29PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/09/28PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/09/27PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/09/26PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/09/25PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Metabolomic profiling identifies novel biomarkers and mechanisms in human bladder cancer treated with submucosal injection of gemcitabine. Int J Mol Med. 2019 Sep 23;: Authors: Yang C, Sun X, Wang H, Lu T, Wu K, Guan Y, Tang J, Liang J, Sun R, Guo Z, Zheng S, Wu X, Jiang H, Jiang X, Zhong B, Niu X, Sun S, Wang X, Chen M, Fu G Abstract Bladder cancer (BCa) is a common urinary tract malignancy with frequent recurrences after initial resection. Submucosal injection of gemcitabine prior to transurethral resection of bladder tumor (TURBT) may prevent recurrence of urothelial cancer. However, the underlying mechanism remains unknown. In the present study, ultra‑performance liquid chromatography Q‑Exactive mass spectrometry was used to profile tissue metabolites from 12 BCa patients. The 48 samples included pre‑ and post‑gemcitabine treatment BCa tissues, as well as adjacent normal tissues. Principal component analysis (PCA) revealed that the metabolic profiles of pre‑gemcitabine BCa tissues differed significantly from those of pre‑gemcitabine normal tissues. A total of 34 significantly altered metabolites were further analyzed. Pathway analysis using MetaboAnalyst identified three metabolic pathways closely associated with BCa, including glutathione, purine and thiamine metabolism, while glutathione metabolism was also identified by the enrichment analysis using MetaboAnalyst. In search of the possible targets of gemcitabine, metabolite profiles were compared between the pre‑gemcitabine normal and post‑gemcitabine BCa tissues. Among the 34 metabolites associated with BCa, the levels of bilirubin and retinal recovered in BCa tissues treated with gemcitabine. When comparing normal bladder tissues with and without gemcitabine treatment, among the 34 metabolites associated with BCa, it was observed that histamine change may be associated with the prevention of relapse, whereas thiamine change may be involved in possible side effects. Therefore, by employing a hypothesis‑free tissue‑based metabolomics study, the present study investigated the metabolic signatures of BCa and found that bilirubin and retinal may be involved in the mechanism underlying the biomolecular action of submucosal injection of gemcitabine in urothelial BCa. PMID: 31545404 [PubMed - as supplied by publisher]

Related Articles Metabolomics and Microbial Composition Increase Insight into the Impact of Dietary Differences in Cirrhosis. Liver Int. 2019 Sep 23;: Authors: Cox IJ, Idiliman R, Fagan A, Turan D, Ajayi L, Le Guennec AD, Taylor-Robinson SD, Karakaya F, Gavis E, Andrew Atkinson R, Williams R, Sikaroodi M, Nizam S, Gillevet PM, Bajaj JS Abstract BACKGROUND & AIMS: Dietary changes can modulate gut microbiota and interact with cirrhosis. Our prior study demonstrated that microbial diversity was higher in Turkish versus USA cirrhotics, which was associated with lower risk of 90-day hospitalizations. We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets. METHODS: 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied. Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake while Americans consumed a Western diet. Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries. Correlation network differences between microbiota and metabolites in cirrhotics from Turkey versus USA were evaluated. RESULTS: Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in Turkey compared to USA cirrhotics. Plasma metabolomics demonstrated higher relative lactate levels in Turkey versus USA. The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and USA, with reduced lipids and phosphocholines. Phosphocholines were significantly lower in patients hospitalized in 90 days (p=0.03). Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients. CONCLUSIONS: A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis. These altered diet-microbial interactions could potentially affect the 90-day hospitalization risk. PMID: 31544308 [PubMed - as supplied by publisher]

Related Articles Characterization of chemical constituents and absorbed components, screening the active components of gelanxinning capsule and an evaluation of therapeutic effects by ultrahigh performance liquid chromatography with quadrupole time-of-flight mass spectrometry. J Sep Sci. 2019 Sep 22;: Authors: Gao X, Hu X, Zhang Q, Wang X, Wen X, Wang Y, Zhang Y, Sun W Abstract It revealed the potential biomarker and pathway of gelanxinning capsule on rat model with coronary heart disease, which aims to clarify holistic therapeutic effect and predict quality-markers of gelanxinning capsule. Ultrahigh performance liquid chromatography-mass spectrometry based on metabolomics technique was used to find the biomarkers and related metabolic pathways of coronary heart disease model, which evaluates the intervention effect of gelanxinning capsule. Using serum pharmacochemistry of traditional Chinese medicine and Pearson correlation analysis, effective ingredients in serum is analyzed to characterize the activity of gelanxinning capsule on coronary heart disease under valid state. A total of 20 biomarkers from coronary heart disease were identified and 12 of them were regulated by gelanxinning capsule treatment, which is mainly involved in sphingolipid metabolism and glycerophospholipid metabolism. With the high sensitivity liquid chromatography-mass spectrometry technology, a total of 46 compounds from gelanxinning capsule were identified in vitro and 25 of them were absorbed in blood. The correlation analysis of serum biomarkers and absorbed components was used to find 11 compounds as quality-markers to be responsible for the efficacy of gelanxinning capsule. This strategy was successfully applied to screening of potential mechanism and quality-markers from herbal medicine.<PE-FRONTEND> This article is protected by copyright. All rights reserved. PMID: 31544307 [PubMed - as supplied by publisher]

Related Articles Metabolic Insights Into the Effects of Nutrient Stress on Lactobacillus plantarum B21. Front Mol Biosci. 2019;6:75 Authors: Parlindungan E, May BK, Jones OAH Abstract Lactobacillus plantarum B21 is a strain of lactic acid bacteria first isolated from a fermented meat product from Vietnam. It is also a promising biopreservative with potential use in the food industry as it is a source of a novel bacteriocin (Plantacyclin B21AG) which has inhibitory effects against a wide range of species, including several pathogenic and spoilage strains. Nutrient stress is known to increase the survivability, storage stability, and bacteriocin production capability of L. plantarum B21 during industrial processing. It is however, unknown what the underlying biochemical responses that control these abilities are. This study therefore investigates the metabolite profiles of L. plantarum B21 using NMR spectroscopy and GC-MS to further understand the biochemical responses of this strain to various stress events. Unstressed cells were found to use glucose as their primary energy source with high concentrations of metabolites involved in glycolysis and organic acid synthesis, such as lactic acid, acetic acid, propanoic acid, malic acid, and 2-butenedioic acid being present in these cells. In contrast, large numbers of metabolites involved in amino acid metabolism including alanine, glutamic acid, aspartic acid, valine, proline, and norleucine were upregulated in glucose stressed cells, indicating that they were using amino acids as their main source of energy. Differences in levels of fatty acids, particularly octadecenoic acid, tetracosanoic acid, and 7-hexadecenoic acid were also observed between stressed and unstressed cells. The results from this study provide insight on the biochemical response of this bacterial strain to stresses commonly found during industrial processing. PMID: 31544106 [PubMed]

Related Articles Exploring Radiation Response in Two Head and Neck Squamous Carcinoma Cell Lines Through Metabolic Profiling. Front Oncol. 2019;9:825 Authors: Lindell Jonsson E, Erngren I, Engskog M, Haglöf J, Arvidsson T, Hedeland M, Petterson C, Laurell G, Nestor M Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of cancer worldwide. Radiotherapy, with or without surgery, represents the major approach to curative treatment. However, not all tumors are equally sensitive to irradiation. It is therefore of interest to apply newer system biology approaches (e.g., metabolic profiling) in squamous cancer cells with different radiosensitivities in order to provide new insights on the mechanisms of radiation response. In this study, two cultured HNSCC cell lines from the same donor, UM-SCC-74A and UM-SCC-74B, were first genotyped using Short Tandem Repeat (STR), and assessed for radiation response by the means of clonogenic survival and growth inhibition assays. Thereafter, cells were cultured, irradiated and collected for subsequent metabolic profiling analyses using liquid chromatography-mass spectrometry (LC-MS). STR verified the similarity of UM-SCC-74A and UM-SCC-74B cells, and three independent assays proved UM-SCC-74B to be clearly more radioresistant than UM-SCC-74A. The LC-MS metabolic profiling demonstrated significant differences in the intracellular metabolome of the two cell lines before irradiation, as well as significant alterations after irradiation. The most important differences between the two cell lines before irradiation were connected to nicotinic acid and nicotinamide metabolism and purine metabolism. In the more radiosensitive UM-SCC-74A cells, the most significant alterations after irradiation were linked to tryptophan metabolism. In the more radioresistant UM-SCC-74B cells, the major alterations after irradiation were connected to nicotinic acid and nicotinamide metabolism, purine metabolism, the methionine cycle as well as the serine, and glycine metabolism. The data suggest that the more radioresistant cell line UM-SCC-74B altered the metabolism to control redox-status, manage DNA-repair, and change DNA methylation after irradiation. This provides new insights on the mechanisms of radiation response, which may aid future identification of biomarkers associated with radioresistance of cancer cells. PMID: 31544064 [PubMed]

Related Articles Metabolomics Based Study of the Antileishmanial Activity of Xanthium strumarium Leaf Extract on Promastigotes Phases of Leishmania major by Proton NMR Spectroscopy. Iran J Parasitol. 2019 Apr-Jun;14(2):258-268 Authors: Ahmadi M, Akbari Z, Alikhani M, Hajhossiani R, Zamani Z, Arjmand M Abstract Background: Xanthium strumarium L. is extensively used as a traditional herb to treat many diseases and is also known as a source of phytochemicals. It has been used traditionally to treat trypanosomiasis, malaria fever, eczema, cancer, ulcer, fever, herpes headache, and skin lesion such as leishmaniasis. In this preliminary study, nuclear magnetic resonance (NMR)-metabolomics approaches was used to evaluate the inhibitory effects and metabolic alterations caused by leaf extract of X. strumarium on the stationary phases of promastigotes in Leishmania major. Methods: The promastigotes were cultured in Biochemistry Laboratory at Pasteur Institute of Iran in 2017, stationary phases were obtained from 5 to 6 day-old cultures and treated with different concentrations of the plant's extract. Antileishmanial activity was assayed by MTT method and cell metabolites were extracted. 1H NMR spectroscopy was applied, and outliers were separated using multivariate statistical analysis. Results: The most affected metabolic pathways in the experimental groups were limited to amino sugar and nucleotide sugar metabolism, cyanoamino acid metabolism, starch and sucrose metabolism, butanoate metabolism, and galactose metabolism. Conclusion: The ethanolic leaf extract of X. strumarium is a potent growth inhibitor of Leishmania major and can affect vital metabolic pathways of Leishmania promastigotes. The assay provided new perspectives on the development of novel treatment strategies for leishmanial activity derived from natural products. PMID: 31543914 [PubMed]

Related Articles Multi-Omics Analysis of Fatty Alcohol Production in Engineered Yeasts Saccharomyces cerevisiae and Yarrowia lipolytica. Front Genet. 2019;10:747 Authors: Dahlin J, Holkenbrink C, Marella ER, Wang G, Liebal U, Lieven C, Weber D, McCloskey D, Ebert BE, Herrgård MJ, Blank LM, Borodina I Abstract Fatty alcohols are widely used in various applications within a diverse set of industries, such as the soap and detergent industry, the personal care, and cosmetics industry, as well as the food industry. The total world production of fatty alcohols is over 2 million tons with approximately equal parts derived from fossil oil and from plant oils or animal fats. Due to the environmental impact of these production methods, there is an interest in alternative methods for fatty alcohol production via microbial fermentation using cheap renewable feedstocks. In this study, we aimed to obtain a better understanding of how fatty alcohol biosynthesis impacts the host organism, baker's yeast Saccharomyces cerevisiae or oleaginous yeast Yarrowia lipolytica. Producing and non-producing strains were compared in growth and nitrogen-depletion cultivation phases. The multi-omics analysis included physiological characterization, transcriptome analysis by RNAseq, 13Cmetabolic flux analysis, and intracellular metabolomics. Both species accumulated fatty alcohols under nitrogen-depletion conditions but not during growth. The fatty alcohol-producing Y. lipolytica strain had a higher fatty alcohol production rate than an analogous S. cerevisiae strain. Nitrogen-depletion phase was associated with lower glucose uptake rates and a decrease in the intracellular concentration of acetyl-CoA in both yeast species, as well as increased organic acid secretion rates in Y. lipolytica. Expression of the fatty alcohol-producing enzyme fatty acyl-CoA reductase alleviated the growth defect caused by deletion of hexadecenal dehydrogenase encoding genes (HFD1 and HFD4) in Y. lipolytica. RNAseq analysis showed that fatty alcohol production triggered a cell wall stress response in S. cerevisiae. RNAseq analysis also showed that both nitrogen-depletion and fatty alcohol production have substantial effects on the expression of transporter encoding genes in Y. lipolytica. In conclusion, through this multi-omics study, we uncovered some effects of fatty alcohol production on the host metabolism. This knowledge can be used as guidance for further strain improvement towards the production of fatty alcohols. PMID: 31543895 [PubMed]

Related Articles Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction. Cell Metab. 2019 Sep 17;: Authors: Chen S, Henderson A, Petriello M, Romano KA, Gearing M, Miao J, Schell M, Sandoval-EspinolaEspinola WJ, Tao J, Sha B, Graham M, Crooke R, Kleinridders A, Balskus EP, Rey FE, Morris A, Biddinger SB Abstract The gut-microbe-derived metabolite trimethylamine N-oxide (TMAO) is increased by insulin resistance and associated with several sequelae of metabolic syndrome in humans, including cardiovascular, renal, and neurodegenerative disease. The mechanism by which TMAO promotes disease is unclear. We now reveal the endoplasmic reticulum stress kinase PERK (EIF2AK3) as a receptor for TMAO: TMAO binds to PERK at physiologically relevant concentrations; selectively activates the PERK branch of the unfolded protein response; and induces the transcription factor FoxO1, a key driver of metabolic disease, in a PERK-dependent manner. Furthermore, interventions to reduce TMAO, either by manipulation of the gut microbiota or by inhibition of the TMAO synthesizing enzyme, flavin-containing monooxygenase 3, can reduce PERK activation and FoxO1 levels in the liver. Taken together, these data suggest TMAO and PERK may be central to the pathogenesis of the metabolic syndrome. PMID: 31543404 [PubMed - as supplied by publisher]

Related Articles High-throughput metabolomic analysis predicts mode of action of uncharacterized antimicrobial compounds. Sci Transl Med. 2018 02 21;10(429): Authors: Zampieri M, Szappanos B, Buchieri MV, Trauner A, Piazza I, Picotti P, Gagneux S, Borrell S, Gicquel B, Lelievre J, Papp B, Sauer U Abstract Rapidly spreading antibiotic resistance and the low discovery rate of new antimicrobial compounds demand more effective strategies for early drug discovery. One bottleneck in the drug discovery pipeline is the identification of the modes of action (MoAs) of new compounds. We have developed a rapid systematic metabolome profiling strategy to classify the MoAs of bioactive compounds. The method predicted MoA-specific metabolic responses in the nonpathogenic bacterium Mycobacterium smegmatis after treatment with 62 reference compounds with known MoAs and different metabolic and nonmetabolic targets. We then analyzed a library of 212 new antimycobacterial compounds with unknown MoAs from a drug discovery effort by the pharmaceutical company GlaxoSmithKline (GSK). More than 70% of these new compounds induced metabolic responses in M. smegmatis indicative of known MoAs, seven of which were experimentally validated. Only 8% (16) of the compounds appeared to target unconventional cellular processes, illustrating the difficulty in discovering new antibiotics with different MoAs among compounds used as monotherapies. For six of the GSK compounds with potentially new MoAs, the metabolome profiles suggested their ability to interfere with trehalose and lipid metabolism. This was supported by whole-genome sequencing of spontaneous drug-resistant mutants of the pathogen Mycobacterium tuberculosis and in vitro compound-proteome interaction analysis for one of these compounds. Our compendium of drug-metabolome profiles can be used to rapidly query the MoAs of uncharacterized antimicrobial compounds and should be a useful resource for the drug discovery community. PMID: 29467300 [PubMed - indexed for MEDLINE]