ORCID Profile
0000-0001-6942-5056
Current Organisation
Aalborg Universitet
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Publisher: American Chemical Society (ACS)
Date: 14-07-2017
DOI: 10.1021/ACS.JNATPROD.6B00822
Abstract: Production of chrysogine has been reported from several fungal genera including Penicillium, Aspergillus, and Fusarium. Anthranilic acid and pyruvic acid, which are expected precursors of chrysogine, enhance production of this compound. A possible route for the biosynthesis using these substrates is via a nonribosomal peptide synthetase (NRPS). Through comparative analysis of the NRPSs from genome-sequenced producers of chrysogine we identified a candidate NRPS cluster comprising five additional genes named chry2-6. Deletion of the two-module NRPS (NRPS14 = chry1) abolished chrysogine production in Fusarium graminearum, indicating that the gene cluster is responsible for chrysogine biosynthesis. Overexpression of NRPS14 enhanced chrysogine production, suggesting that the NRPS is the bottleneck in the biosynthetic pathway.
Publisher: Springer Science and Business Media LLC
Date: 22-11-2012
Publisher: Springer Science and Business Media LLC
Date: 08-2019
DOI: 10.1007/S11306-019-1569-3
Abstract: Progressive chronic kidney disease (CKD) is an important cause of morbidity and mortality. It has a long asymptomatic phase, where routine blood tests cannot identify early functional losses, and therefore identifying common mechanisms across the many etiologies is an important goal. Our aim was to characterize serum, urine and tissue (kidney, lung, heart, spleen and liver) metabolomics changes in a rat model of CKD. A total of 17 male Wistar rats underwent 5/6 nephrectomy, whilst 13 rats underwent sham operation. Urine s les were collected weekly, for 6 weeks blood was collected at weeks 0, 3 and 6 and tissue s les were collected at week 6. S les were analyzed on a nuclear magnetic resonance spectroscopy platform with multivariate and univariate data analysis. Changes in several metabolites were statistically significant. Allantoin was affected in all compartments. Renal asparagine, creatine, hippurate and trimethylamine were significantly different in other tissues creatine, dimethylamine, dimethylglycine, trigonelline and trimethylamine were significant. Benzoate, citrate, dimethylglycine, fumarate, guanidinoacetate, malate, myo-inositol and oxoglutarate were altered in urine or serum. Although the metabolic picture is complex, we suggest oxidative stress, the gut-kidney axis, acid-base balance, and energy metabolism as promising areas for future investigation.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2017
DOI: 10.1038/SREP40275
Abstract: Cardiovascular disease is the leading cause of death worldwide and patients with severe symptoms undergo cardiac surgery. Even after uncomplicated surgeries, some patients experience postoperative complications such as lung injury. We hypothesized that the procedure elicits metabolic activity that can be related to the disease progression, which is commonly observed two-three days postoperatively. More than 700 blood s les were collected from 50 patients at nine time points pre-, intra-, and postoperatively. Dramatic metabolite shifts were observed during and immediately after the intervention. Prolonged surgical stress was linked to an augmented anaerobic environment. Time series analysis showed shifts in purine-, nicotinic acid-, tyrosine-, hyaluronic acid-, ketone-, fatty acid, and lipid metabolism. A characteristic ‘metabolic biosignature’ was identified correlating with the risk of developing postoperative complications two days before the first clinical signs of lung injury. Hence, this study demonstrates the link between intra- and postoperative time-dependent metabolite changes and later postoperative outcome. In addition, the results indicate that metabotyping patients’ journeys early, during or just after the end of surgery, may have potential impact in hospitals for the early diagnosis of postoperative lung injury, and for the monitoring of therapeutics targeting disease progression.
Publisher: American Chemical Society (ACS)
Date: 20-11-2014
DOI: 10.1021/NP500436R
Abstract: The closely related species Fusarium graminearum and Fusarium pseudograminearum differ in that each contains a gene cluster with a polyketide synthase (PKS) and a nonribosomal peptide synthetase (NRPS) that is not present in the other species. To identify their products, we deleted PKS6 and NRPS7 in F. graminearum and NRPS32 in F. pseudograminearum. By comparing the secondary metabolite profiles of the strains we identified the resulting product in F. graminearum as fusaristatin A, and as W493 A and B in F. pseudograminearum. These lipopeptides have previously been isolated from unidentified Fusarium species. On the basis of genes in the putative gene clusters we propose a model for biosynthesis where the polyketide product is shuttled to the NPRS via a CoA ligase and a thioesterase in F. pseudograminearum. In F. graminearum the polyketide is proposed to be directly assimilated by the NRPS.
Publisher: IEEE
Date: 11-2017
Publisher: MDPI AG
Date: 21-11-2018
DOI: 10.3390/JCM7110462
Abstract: Cardiac surgery with cardiopulmonary bypass (CPB) causes an acute lung ischemia-reperfusion injury, which can develop to pulmonary dysfunction postoperatively. This sub-study of the Pulmonary Protection Trial aimed to elucidate changes in arterial blood gas analyses, inflammatory protein interleukin-6, and metabolites of 90 chronic obstructive pulmonary disease patients following two lung protective regimens of pulmonary artery perfusion with either hypothermic histidine-tryptophan-ketoglutarate (HTK) solution or normothermic oxygenated blood during CPB, compared to the standard CPB with no pulmonary perfusion. Blood was collected at six time points before, during, and up to 20 h post-CPB. Blood gas analysis, enzyme-linked immunosorbent assay, and nuclear magnetic resonance spectroscopy were used, and multivariate and univariate statistical analyses were performed. All patients had decreased gas exchange, augmented inflammation, and metabolite alteration during and after CPB. While no difference was observed between patients receiving oxygenated blood and standard CPB, patients receiving HTK solution had an excess of metabolites involved in energy production and detoxification of reactive oxygen species. Also, patients receiving HTK suffered a transient isotonic hyponatremia that resolved within 20 h post-CPB. Additional studies are needed to further elucidate how to diminish lung ischemia-reperfusion injury during CPB, and thereby, reduce the risk of developing severe postoperative pulmonary dysfunction.
Publisher: Springer Science and Business Media LLC
Date: 24-06-2020
DOI: 10.1038/S41597-020-0545-0
Abstract: Cardiovascular disease is the leading cause of death worldwide and cardiac surgery is a key treatment. This study explores metabolite changes as a consequence of ischemia-reperfusion due to cardiac surgery with the use of cardiopulmonary bypass (CPB). To describe the ischemia-reperfusion injury, metabolite changes were monitored in fifty patients before and after CPB at multiple time points. We describe a longitudinal metabolite dataset containing nearly 600 serum nuclear magnetic resonance (NMR) spectra obtained from s les collected simultaneously from the pulmonary artery (deoxygenated blood) and left atrium (oxygenated blood) before ischemia (pre-CPB), immediately after reperfusion (end-CPB), and the following 2, 4, 8, and 20 hours postoperatively. In addition, a longitudinal dataset including 57 quantified metabolites is also provided. These datasets will help researchers studying ischemia-reperfusion injury, as well as the time-dependent alterations related to the surgical trauma and the subsequent processes required in regaining metabolite balance. The datasets could also be used for the development of processing algorithms for NMR-based metabolomics studies and methods for the analysis of longitudinal multivariate data.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2016
Publisher: Springer Science and Business Media LLC
Date: 19-12-2019
DOI: 10.1007/S11306-019-1629-8
Abstract: In our metabolomics studies we have noticed that repeated NMR acquisition on the same s le can result in altered metabolite signal intensities. To investigate the reproducibility of repeated NMR acquisition on selected metabolites in serum and plasma from two large human metabolomics studies. Two peak regions for each metabolite were integrated and changes occurring after reacquisition were correlated. Integral changes were generally small, but serum citrate signals decreased significantly in some s les. Several metabolite integrals were not reproducible in some of the repeated spectra. Following established protocols, randomising analysis order and biomarker validation are important.
Publisher: Wiley
Date: 24-10-2017
DOI: 10.1111/MPP.12593
Publisher: MDPI AG
Date: 21-09-2018
Abstract: Pulmonary dysfunction is among the most frequent complications to cardiac surgeries. Exposure of blood to the cardiopulmonary bypass (CPB) circuit with subsequent lung ischemia-reperfusion leads to the production of inflammatory mediators and increases in microvascular permeability. The study aimed to elucidate histological, cellular, and metabolite changes following two lung protective regimens during CPB with Histidine-Tryptophan-Ketoglutarate (HTK) enriched or warm oxygenated blood pulmonary perfusion compared to standard regimen with no pulmonary perfusion. A total of 90 patients undergoing CPB were randomized to receiving HTK, oxygenated blood or standard regimen. Of these, bronchoalveolar lavage fluid (BALF) and lung tissue biopsies were obtained before and after CPB from 47 and 25 patients, respectively. Histopathological scores, BALF cell counts and metabolite screening were assessed. Multivariate and univariate analyses were performed. Profound histological, cellular, and metabolic changes were identified in all patients after CPB. Histological and cellular changes were similar in the three groups however, some metabolite profiles were different in the HTK patients. While all patients presented an increase in inflammatory cells, metabolic acidosis, protease activity and oxidative stress, HTK patients seemed to be protected against severe acidosis, excessive fatty acid oxidation, and inflammation during ischemia-reperfusion. Additional studies are needed to confirm these findings.
No related grants have been discovered for Reinhard Wimmer.