Chapter 2. Chemical Derivatization for Polar Metabolome Analysis

Abstract Background Fusarium head blight is a disease of global concern that reduces crop yields and renders grains unfit for consumption due to mycotoxin contamination. Fusarium poae is frequently associated with cereal crops showing symptoms of Fusarium head blight. While previous studies have shown F. poae isolates produce a range of known mycotoxins, including type A and B trichothecenes, fusarins and beauvericin, genomic analysis suggests that this species may have lineage-specific accessory chromosomes with secondary metabolite biosynthetic gene clusters awaiting description. Methods We examined the biosynthetic potential of 38 F. poae isolates from Eastern Canada using a combination of long-read and short-read genome sequencing and untargeted, high resolution mass spectrometry metabolome analysis of extracts from isolates cultured in multiple media conditions. Results A high-quality assembly of isolate DAOMC 252244 (Fp157) contained four core chromosomes as well as seven additional contigs with traits associated with accessory chromosomes. One of the predicted accessory contigs harbours a functional biosynthetic gene cluster containing homologs of all genes associated with the production of apicidins. Metabolomic and genomic analyses confirm apicidins are produced in 4 of the 38 isolates investigated and genomic PCR screening detected the apicidin synthetase gene APS1 in approximately 7% of Eastern Canadian isolates surveyed. Conclusions Apicidin biosynthesis is linked to isolate-specific putative accessory chromosomes in F. poae. The data produced here are an important resource for furthering our understanding of accessory chromosome evolution and the biosynthetic potential of F. poae.

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Large-scale plasma-metabolome analysis identifies potential biomarkers of psoriasis and its clinical subtypes

Journal of Dermatological Science ◽

10.1016/j.jdermsci.2021.03.006 ◽

2021 ◽

Author(s):

Toshihiro Kishikawa ◽

Noriko Arase ◽

Shigeyoshi Tsuji ◽

Yuichi Maeda ◽

Takuro Nii ◽

...

Keyword(s):

Large Scale ◽

Metabolome Analysis ◽

Plasma Metabolome ◽

Potential Biomarkers

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Comparative untargeted metabolome analysis of ruminal fluid and feces of Nelore steers (Bos indicus)

Scientific Reports ◽

10.1038/s41598-021-92179-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jessica Moraes Malheiros ◽

Banny Silva Barbosa Correia ◽

Caroline Ceribeli ◽

Daniel Rodrigues Cardoso ◽

Luiz Alberto Colnago ◽

...

Keyword(s):

Ketone Bodies ◽

Rumen Fluid ◽

Bos Indicus ◽

Metabolite Profile ◽

Polar Compounds ◽

Metabolome Analysis ◽

Ruminal Fluid ◽

Polar Metabolites ◽

Close Relationship ◽

Synthesis And Degradation

AbstractWe conducted a study to identify the fecal metabolite profile and its proximity to the ruminal metabolism of Nelore steers based on an untargeted metabolomic approach. Twenty-six Nelore were feedlot with same diet during 105 d. Feces and rumen fluid were collected before and at slaughter, respectively. The metabolomics analysis indicated 49 common polar metabolites in the rumen and feces. Acetate, propionate, and butyrate were the most abundant polar metabolites in both bio-samples. The rumen presented significantly higher concentrations of the polar compounds when compared to feces (P < 0.05); even though, fecal metabolites presented an accentuated representability of the ruminal fluid metabolites. All fatty acids present in the ruminal fluid were also observed in the feces, except for C20:2n6 and C20:4n6. The identified metabolites offer information on the main metabolic pathways (higher impact factor and P < 0.05), as synthesis and degradation of ketone bodies; the alanine, aspartate and glutamate metabolisms, the glycine, serine; and threonine metabolism and the pyruvate metabolism. The findings reported herein on the close relationship between the ruminal fluid and feces metabolic profiles may offer new metabolic information, in addition to facilitating the sampling for metabolism investigation in animal production and health routines.

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Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma

Cells ◽

10.3390/cells10071821 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1821

Author(s):

Ujjwal Mukund Mahajan ◽

Ahmed Alnatsha ◽

Qi Li ◽

Bettina Oehrle ◽

Frank-Ulrich Weiss ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Enrichment Analysis ◽

Response Prediction ◽

Ductal Adenocarcinoma ◽

Pathway Enrichment Analysis ◽

Metabolome Analysis ◽

Dismal Prognosis ◽

Chemotherapeutic Response ◽

Plasma Metabolome ◽

Metabolome Profiling

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Developing biomarkers for early detection and chemotherapeutic response prediction is crucial to improve the dismal prognosis of PDAC patients. However, molecular cancer signatures based on transcriptome analysis do not reflect intratumoral heterogeneity. To explore a more accurate stratification of PDAC phenotypes in an easily accessible matrix, plasma metabolome analysis using MxP® Global Profiling and MxP® Lipidomics was performed in 361 PDAC patients. We identified three metabolic PDAC subtypes associated with distinct complex lipid patterns. Subtype 1 was associated with reduced ceramide levels and a strong enrichment of triacylglycerols. Subtype 2 demonstrated increased abundance of ceramides, sphingomyelin and other complex sphingolipids, whereas subtype 3 showed decreased levels of sphingolipid metabolites in plasma. Pathway enrichment analysis revealed that sphingolipid-related pathways differ most among subtypes. Weighted correlation network analysis (WGCNA) implied PDAC subtypes differed in their metabolic programs. Interestingly, a reduced expression among related pathway genes in tumor tissue was associated with the lowest survival rate. However, our metabolic PDAC subtypes did not show any correlation to the described molecular PDAC subtypes. Our findings pave the way for further studies investigating sphingolipids metabolisms in PDAC.

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Nicotinamide Effectively Suppresses Fusarium Head Blight in Wheat Plants

International Journal of Molecular Sciences ◽

10.3390/ijms22062968 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2968

Author(s):

Yasir Sidiq ◽

Masataka Nakano ◽

Yumi Mori ◽

Takashi Yaeno ◽

Makoto Kimura ◽

...

Keyword(s):

Fusarium Head Blight ◽

Fungal Pathogen ◽

Antifungal Compounds ◽

Pyridine Nucleotides ◽

Fungal Metabolites ◽

Dna Hypomethylation ◽

Metabolome Analysis ◽

Head Blight ◽

Ergosterol Peroxide ◽

Nicotinamide Mononucleotide

Pyridine nucleotides such as a nicotinamide adenine dinucleotide (NAD) are known as plant defense activators. We previously reported that nicotinamide mononucleotide (NMN) enhanced disease resistance against fungal pathogen Fusarium graminearum in barley and Arabidopsis. In this study, we reveal that the pretreatment of nicotinamide (NIM), which does not contain nucleotides, effectively suppresses disease development of Fusarium Head Blight (FHB) in wheat plants. Correspondingly, deoxynivalenol (DON) mycotoxin accumulation was also significantly decreased by NIM pretreatment. A metabolome analysis showed that several antioxidant and antifungal compounds such as trigonelline were significantly accumulated in the NIM-pretreated spikes after inoculation of F. graminearum. In addition, some metabolites involved in the DNA hypomethylation were accumulated in the NIM-pretreated spikes. On the other hand, fungal metabolites DON and ergosterol peroxide were significantly reduced by the NIM pretreatment. Since NIM is relative stable and inexpensive compared with NMN and NAD, it may be more useful for the control of symptoms of FHB and DON accumulation in wheat and other crops.

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Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma

Endocrinology ◽

10.1210/en.2018-00014 ◽

2018 ◽

Vol 159 (8) ◽

pp. 2836-2849 ◽

Cited By ~ 8

Author(s):

Vasileios Chortis ◽

Angela E Taylor ◽

Craig L Doig ◽

Mark D Walsh ◽

Eirini Meimaridou ◽

...

Keyword(s):

Oxidative Stress ◽

Adrenocortical Carcinoma ◽

Reduced Form ◽

Polyamine Metabolism ◽

Metabolome Analysis ◽

Nucleotide Synthesis ◽

Treatment Target ◽

Nicotinamide Nucleotide Transhydrogenase ◽

Response To Chemotherapy

Abstract Adrenocortical carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. In this study, we evaluated a potential new treatment target for ACC, focusing on the mitochondrial reduced form of NAD phosphate (NADPH) generator nicotinamide nucleotide transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating human NNT mutations result in congenital adrenal insufficiency. We hypothesized that NNT silencing in ACC cells will induce toxic levels of oxidative stress. To explore this, we transiently knocked down NNT in NCI-H295R ACC cells. As predicted, this manipulation increased intracellular levels of oxidative stress; this resulted in a pronounced suppression of cell proliferation and higher apoptotic rates, as well as sensitization of cells to chemically induced oxidative stress. Steroidogenesis was paradoxically stimulated by NNT loss, as demonstrated by mass spectrometry–based steroid profiling. Next, we generated a stable NNT knockdown model in the same cell line to investigate the longer lasting effects of NNT silencing. After long-term culture, cells adapted metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remained suppressed. This was associated with higher rates of oxygen consumption. The molecular pathways underpinning these responses were explored in detail by RNA sequencing and nontargeted metabolome analysis, revealing major alterations in nucleotide synthesis, protein folding, and polyamine metabolism. This study provides preclinical evidence of the therapeutic merit of antioxidant targeting in ACC as well as illuminating the long-term adaptive response of cells to oxidative stress.

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AB0185 PROSPECTIVE PROFILE OF URINE METABOLOME IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4481 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1392.2-1392

Author(s):

M. De Oliveira ◽

P. V. Alabarse ◽

M. Farinon ◽

R. Cavalheiro Do Espírito Santo ◽

R. Xavier

Keyword(s):

Rheumatoid Arthritis ◽

Skeletal Muscle ◽

Disease Activity ◽

Pearson Correlation ◽

Statistical Significance ◽

Resonance Spectroscopy ◽

Metabolome Analysis ◽

Orthogonal Projections ◽

Urine Metabolome

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality and associated with metabolic disorders. Since the metabolomic profile is known to vary in response to different inflammatory conditions, metabolome analysis could substantially improve diagnosis and prognosis of RA.Objectives:To analyze the urine metabolome profile in RA patients and correlate it with disease activity changes over 12 monthsMethods:Seventy-nine RA patients, according to ACR/EULAR 2010 classification criteria, between 40 and 70 years old, were recruited and followed for 12 months. Metabolome analysis was performed by Nuclear Magnetic Resonance spectroscopy (NMR), resulting in the identification of 93 metabolites in urine collected at the baseline and after 12 months. Frequency analysis, Pearson Correlation and Multivariate data analysis with orthogonal projections to latent structures (OPLS) method were performed and a statistical significance was considered as p<0.05.Results:The study population was characterized by the majority of women (86.7%), mean age of 56 years old, around 80% with positive anti-CCP or Rheumatoid Factor. During the one year of follow-up, there was no substantial variation in the DAS28 measurement (baseline: 3.8, after 12 months: 4.0). There was no significant correlation between the metabolome pattern and DAS28 score (p>0.05) over time. However, multivariate analysis (OPLS-DA) demonstrated an adequate differentiation of the population with 0.92 of accuracy (Q2: 0.72 and R2: 0.89).There was a significant increase of L-cysteine, choline, L-Phenylalanin, creatine, L-histidine, oxalacetic acid and xanthine, and a decrease of L-threonine, taurine, butyric and gluconic acid (p<0.05) during the follow-up, metabolites that are involved in the skeletal muscle metabolism.Conclusion:The observed biomarkers indicate,as expected, that the RA metabolic profile is associated with inflammation injury and skeletal muscle amino acid metabolism. Correlations with disease activity changes was compromised by the stable disease status during the 12 months. More studies evaluating correlations with skeletal muscle function and mass are underway.Acknowledgments:Disclosure of interest: Marianne Oliveira: None declared, Rafaela Santo: None declared, Mirian Farinon: None declared, Ricardo Xavier Consultant of: Abbvie, Pfizer, Novartis, Janssen, Lilly, RocheDisclosure of Interests:Marianne de Oliveira: None declared, Paulo Vinicius Alabarse: None declared, Mirian Farinon: None declared, Rafaela Cavalheiro do Espírito Santo: None declared, Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche

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