Alcoholic beverages are produced following the fermentation of sugars by yeasts, mainly (but not exclusively) strains of the species, Saccharomyces cerevisiae. The sugary starting materials may ...emanate from cereal starches (which require enzymatic pre-hydrolysis) in the case of beers and whiskies, sucrose-rich plants (molasses or sugar juice from sugarcane) in the case of rums, or from fruits (which do not require pre-hydrolysis) in the case of wines and brandies. In the presence of sugars, together with other essential nutrients such as amino acids, minerals and vitamins, S. cerevisiae will conduct fermentative metabolism to ethanol and carbon dioxide (as the primary fermentation metabolites) as the cells strive to make energy and regenerate the coenzyme NAD+ under anaerobic conditions. Yeasts will also produce numerous secondary metabolites which act as important beverage flavour congeners, including higher alcohols, esters, carbonyls and sulphur compounds. These are very important in dictating the final flavour and aroma characteristics of beverages such as beer and wine, but also in distilled beverages such as whisky, rum and brandy. Therefore, yeasts are of vital importance in providing the alcohol content and the sensory profiles of such beverages. This Introductory Chapter reviews, in general, the growth, physiology and metabolism of S. cerevisiae in alcoholic beverage fermentations.
This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of ...mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer's disease (MCI_AD; n = 19), and healthy age-matched controls (Ctrl; n = 37). Plasma was extracted in acetonitrile and applied to an Acquity UPLC HILIC (1.7μm x 2.1 x 100 mm) column coupled to a Xevo G2 QTof mass spectrometer using a previously optimised method. Data comprising 6751 spectral features were used to build an OPLS-DA statistical model capable of accurately distinguishing Ctrl, MCI and MCI_AD. The model accurately distinguished (R2 = 99.1%; Q2 = 97%) those MCI patients who later went on to develop AD. S-plots were used to shortlist ions of interest which were responsible for explaining the maximum amount of variation between patient groups. Metabolite database searching and pathway enrichment analysis indicated disturbances in 22 biochemical pathways, and excitingly it discovered two interlinked areas of metabolism (polyamine metabolism and L-Arginine metabolism) were differentially disrupted in this well-defined clinical cohort. The optimised untargeted HRMS methods described herein not only demonstrate that it is possible to distinguish these pathologies in human blood but also that MCI patients 'at risk' from AD could be predicted up to 2 years earlier than conventional clinical diagnosis. Blood-based metabolite profiling of plasma from memory clinic patients is a novel and feasible approach in improving MCI and AD diagnosis and, refining clinical trials through better patient stratification.
Free Amino Nitrogen in Brewing Hill, Annie E.; Stewart, Graham G.
Fermentation (Basel),
02/2019, Letnik:
5, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The role of nitrogenous components in malt and wort during the production of beer has long been recognized. The concentration and range of wort amino acids impact on ethanolic fermentation by yeast ...and on the production of a range of flavour and aroma compounds in the final beer. This review summarizes research on Free Amino Nitrogen (FAN) within brewing, including various methods of analysis.
To interrogate the pathogenesis of intrauterine growth restriction (IUGR) and apply Artificial Intelligence (AI) techniques to multi-platform i.e. nuclear magnetic resonance (NMR) spectroscopy and ...mass spectrometry (MS) based metabolomic analysis for the prediction of IUGR.
MS and NMR based metabolomic analysis were performed on cord blood serum from 40 IUGR (birth weight < 10th percentile) cases and 40 controls. Three variable selection algorithms namely: Correlation-based feature selection (CFS), Partial least squares regression (PLS) and Learning Vector Quantization (LVQ) were tested for their diagnostic performance. For each selected set of metabolites and the panel consists of metabolites common in three selection algorithms so-called overlapping set (OL), support vector machine (SVM) models were developed for which parameter selection was performed busing 10-fold cross validations. Area under the receiver operating characteristics curve (AUC), sensitivity and specificity values were calculated for IUGR diagnosis. Metabolite set enrichment analysis (MSEA) was performed to identify which metabolic pathways were perturbed as a direct result of IUGR in cord blood serum.
All selected metabolites and their overlapping set achieved statistically significant accuracies in the range of 0.78-0.82 for their optimized SVM models. The model utilizing all metabolites in the dataset had an AUC = 0.91 with a sensitivity of 0.83 and specificity equal to 0.80. CFS and OL (Creatinine, C2, C4, lysoPC.a.C16.1, lysoPC.a.C20.3, lysoPC.a.C28.1, PC.aa.C24.0) showed the highest performance with sensitivity (0.87) and specificity (0.87), respectively. MSEA revealed significantly altered metabolic pathways in IUGR cases. Dysregulated pathways include: beta oxidation of very long fatty acids, oxidation of branched chain fatty acids, phospholipid biosynthesis, lysine degradation, urea cycle and fatty acid metabolism.
A systematically selected panel of metabolites was shown to accurately detect IUGR in newborn cord blood serum. Significant disturbance of hepatic function and energy generating pathways were found in IUGR cases.
Tumour angiogenesis is an important hallmark of cancer and the study of its metabolic adaptations, downstream to any cellular change, can reveal attractive targets for inhibiting cancer growth. In ...the tumour microenvironment, endothelial cells (ECs) interact with heterogeneous tumour cell types that drive angiogenesis and metastasis. In this study we aim to characterize the metabolic alterations in ECs influenced by the presence of tumour cells with extreme metastatic abilities. Human umbilical vein endothelial cells (HUVECs) were subjected to different microenvironmental conditions, such as the presence of highly metastatic PC-3M and highly invasive PC-3S prostate cancer cell lines, in addition to the angiogenic activator vascular endothelial growth factor (VEGF), under normoxia. Untargeted high resolution liquid chromatography-mass spectrometry (LC-MS) based metabolomics revealed significant metabolite differences among the various conditions and a total of 25 significantly altered metabolites were identified including acetyl L-carnitine, NAD+, hypoxanthine, guanine and oleamide, with profile changes unique to each of the experimental conditions. Biochemical pathway analysis revealed the importance of fatty acid oxidation and nucleotide salvage pathways. These results provide a global metabolic preview that could help in selectively targeting the ECs aiding in either cancer cell invasion or metastasis in the heterogeneous tumour microenvironment.
Ethanol, carbon dioxide and glycerol are the major products produced by yeast during wort fermentation but they have little impact on beer and spirit flavour. It is the type and concentration of ...secondary metabolites that can determine overall beer flavour. These compounds are (but not only) primarily: higher alcohols, esters, carbonyls and sulphur compounds—inorganic and organic. There are a number of factors that can modify the balance of these compounds most of which are discussed in this review paper.
The characteristic flavour and aroma of any beer is, in large part, determined by the yeast strain employed and the wort composition. In addition, properties such as flocculation, wort fermentation ...ability (including the uptake of wort sugars, amino acids, and peptides), ethanol and osmotic pressure tolerance together with oxygen requirements have a critical impact on fermentation performance. Yeast management between fermentations is also a critical brewing parameter. Brewer’s yeasts are mostly part of the genus Saccharomyces. Ale yeasts belong to the species Saccharomyces cerevisiae and lager yeasts to the species Saccharomyces pastorianus. The latter is an interspecies hybrid between S. cerevisiae and Saccharomyces eubayanus. Brewer’s yeast strains are facultative anaerobes—they are able to grow in the presence or absence of oxygen and this ability supports their property as an important industrial microorganism. This article covers important aspects of Saccharomyces molecular biology, physiology, and metabolism that is involved in wort fermentation and beer production.
Parkinson's disease is the second most common neurodegenerative disease. In the vast majority of cases the origin is not genetic and the cause is not well understood, although progressive ...accumulation of α-synuclein aggregates appears central to the pathogenesis. Currently, treatments that slow disease progression are lacking, and there are no robust biomarkers that can facilitate the development of such treatments or act as aids in early diagnosis. Therefore, we have defined metabolomic changes in the brain and serum in an animal model of prodromal Parkinson's disease. We biochemically profiled the brain tissue and serum in a mouse model with progressive synucleinopathy propagation in the brain triggered by unilateral injection of preformed α-synuclein fibrils in the olfactory bulb. In total, we accurately identified and quantified 71 metabolites in the brain and 182 in serum using
H NMR and targeted mass spectrometry, respectively. Using multivariate analysis, we accurately identified which metabolites explain the most variation between cases and controls. Using pathway enrichment analysis, we highlight significantly perturbed biochemical pathways in the brain and correlate these with the progression of the disease. Furthermore, we identified the top six discriminatory metabolites and were able to develop a model capable of identifying animals with the pathology from healthy controls with high accuracy (AUC (95% CI) = 0.861 (0.755-0.968)). Our study highlights the utility of metabolomics in identifying elements of Parkinson's disease pathogenesis and for the development of early diagnostic biomarkers of the disease.
ADP-ribosyltransferases use NAD
to catalyse substrate ADP-ribosylation
, and thereby regulate cellular pathways or contribute to toxin-mediated pathogenicity of bacteria
. Reversible ADP-ribosylation ...has traditionally been considered a protein-specific modification
, but recent in vitro studies have suggested nucleic acids as targets
. Here we present evidence that specific, reversible ADP-ribosylation of DNA on thymidine bases occurs in cellulo through the DarT-DarG toxin-antitoxin system, which is found in a variety of bacteria (including global pathogens such as Mycobacterium tuberculosis, enteropathogenic Escherichia coli and Pseudomonas aeruginosa)
. We report the structure of DarT, which identifies this protein as a diverged member of the PARP family. We provide a set of high-resolution structures of this enzyme in ligand-free and pre- and post-reaction states, which reveals a specialized mechanism of catalysis that includes a key active-site arginine that extends the canonical ADP-ribosyltransferase toolkit. Comparison with PARP-HPF1, a well-established DNA repair protein ADP-ribosylation complex, offers insights into how the DarT class of ADP-ribosyltransferases evolved into specific DNA-modifying enzymes. Together, our structural and mechanistic data provide details of this PARP family member and contribute to a fundamental understanding of the ADP-ribosylation of nucleic acids. We also show that thymine-linked ADP-ribose DNA adducts reversed by DarG antitoxin (functioning as a noncanonical DNA repair factor) are used not only for targeted DNA damage to induce toxicity, but also as a signalling strategy for cellular processes. Using M. tuberculosis as an exemplar, we show that DarT-DarG regulates growth by ADP-ribosylation of DNA at the origin of chromosome replication.
Unlike most fermentation alcohol beverage production processes, brewers recycle their yeast. This is achieved by employing a yeast culture’s: flocculation, adhesion, sedimentation, flotation, and ...cropping characteristics. As a consequence of yeast recycling, the quality of the cropped yeast culture’s characteristics is critical. However, the other major function of brewer’s yeast is to metabolise wort into ethanol, carbon dioxide, glycerol, and other fermentation products, many of which contribute to beer’s overall flavour characteristics. This review will only focus on brewer’s yeast flocculation characteristics.
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