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Microbiology and Molecular Biology... Dec 2021Accumulation of phosphorylated intermediates during cellular metabolism can have wide-ranging toxic effects on many organisms, including humans and the pathogens that...
Accumulation of phosphorylated intermediates during cellular metabolism can have wide-ranging toxic effects on many organisms, including humans and the pathogens that infect them. These toxicities can be induced by feeding an upstream metabolite (a sugar, for instance) while simultaneously blocking the appropriate metabolic pathway with either a mutation or an enzyme inhibitor. Here, we survey the toxicities that can arise in the metabolism of glucose, galactose, fructose, fructose-asparagine, glycerol, trehalose, maltose, mannose, mannitol, arabinose, and rhamnose. Select enzymes in these metabolic pathways may serve as novel therapeutic targets. Some are conserved broadly among prokaryotes and eukaryotes (e.g., glucose and galactose) and are therefore unlikely to be viable drug targets. However, others are found only in bacteria (e.g., fructose-asparagine, rhamnose, and arabinose), and one is found in fungi but not in humans (trehalose). We discuss what is known about the mechanisms of toxicity and how resistance is achieved in order to identify the prospects and challenges associated with targeted exploitation of these pervasive metabolic vulnerabilities.
Topics: Arabinose; Galactose; Humans; Lactose; Phosphates; Xylose
PubMed: 34585982
DOI: 10.1128/MMBR.00123-21 -
Extremophiles : Life Under Extreme... Mar 2008In spite of their common hypersaline environment, halophilic archaea are surprisingly different in their nutritional demands and metabolic pathways. The metabolic... (Comparative Study)
Comparative Study Review
In spite of their common hypersaline environment, halophilic archaea are surprisingly different in their nutritional demands and metabolic pathways. The metabolic diversity of halophilic archaea was investigated at the genomic level through systematic metabolic reconstruction and comparative analysis of four completely sequenced species: Halobacterium salinarum, Haloarcula marismortui, Haloquadratum walsbyi, and the haloalkaliphile Natronomonas pharaonis. The comparative study reveals different sets of enzyme genes amongst halophilic archaea, e.g. in glycerol degradation, pentose metabolism, and folate synthesis. The carefully assessed metabolic data represent a reliable resource for future system biology approaches as it also links to current experimental data on (halo)archaea from the literature.
Topics: Euryarchaeota; Folic Acid; Genome, Archaeal; Glycerol; Pentoses
PubMed: 18278431
DOI: 10.1007/s00792-008-0138-x -
Applied Microbiology and Biotechnology Mar 2011L-Arabinose is the second most abundant pentose beside D-xylose and is found in the plant polysaccharides, hemicellulose and pectin. The need to find renewable carbon... (Review)
Review
L-Arabinose is the second most abundant pentose beside D-xylose and is found in the plant polysaccharides, hemicellulose and pectin. The need to find renewable carbon and energy sources has accelerated research to investigate the potential of L-arabinose for the development and production of biofuels and other bioproducts. Fungi produce a number of extracellular arabinanases, including α-L-arabinofuranosidases and endo-arabinanases, to specifically release L-arabinose from the plant polymers. Following uptake of L-arabinose, its intracellular catabolism follows a four-step alternating reduction and oxidation path, which is concluded by a phosphorylation, resulting in D-xylulose 5-phosphate, an intermediate of the pentose phosphate pathway. The genes and encoding enzymes L-arabinose reductase, L-arabinitol dehydrogenase, L-xylulose reductase, xylitol dehydrogenase, and xylulokinase of this pathway were mainly characterized in the two biotechnological important fungi Aspergillus niger and Trichoderma reesei. Analysis of the components of the L-arabinose pathway revealed a number of specific adaptations in the enzymatic and regulatory machinery towards the utilization of L-arabinose. Further genetic and biochemical analysis provided evidence that L-arabinose and the interconnected D-xylose pathway are also involved in the oxidoreductive degradation of the hexose D-galactose.
Topics: Arabinose; Aspergillus niger; Metabolic Networks and Pathways; Polysaccharides; Trichoderma
PubMed: 21212945
DOI: 10.1007/s00253-010-3071-8 -
Biotechnology Journal Jan 2019Extending the host substrate range of industrially relevant microbes, such as Saccharomyces cerevisiae, has been a highly-active area of research since the conception of... (Review)
Review
Extending the host substrate range of industrially relevant microbes, such as Saccharomyces cerevisiae, has been a highly-active area of research since the conception of metabolic engineering. Yet, rational strategies that enable non-native substrate utilization in this yeast without the need for combinatorial and/or evolutionary techniques are underdeveloped. Herein, this review focuses on pentose metabolism in S. cerevisiae as a case study to highlight the challenges in this field. In the last three decades, work has focused on expressing exogenous pentose metabolizing enzymes as well as endogenous enzymes for effective pentose assimilation, growth, and biofuel production. The engineering strategies that are employed for pentose assimilation in this yeast are reviewed, and compared with metabolism and regulation of native sugar, galactose. In the case of galactose metabolism, multiple signals regulate and aid growth in the presence of the sugar. However, for pentoses that are non-native, it is unclear if similar growth and regulatory signals are activated. Such a comparative analysis aids in identifying missing links in xylose and arabinose utilization. While research on pentose metabolism have mostly concentrated on pathway level optimization, recent transcriptomics analyses highlight the need to consider more global regulatory, structural, and signaling components.
Topics: Arabinose; Galactose; Metabolic Engineering; Pentoses; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Systems Biology
PubMed: 30171750
DOI: 10.1002/biot.201800364 -
Environmental Microbiology Feb 2023The Pseudomonas putida group in the Gammaproteobacteria has been intensively studied for bioremediation and plant growth promotion. Members of this group have recently...
The Pseudomonas putida group in the Gammaproteobacteria has been intensively studied for bioremediation and plant growth promotion. Members of this group have recently emerged as promising hosts to convert intermediates derived from plant biomass to biofuels and biochemicals. However, most strains of P. putida cannot metabolize pentose sugars derived from hemicellulose. Here, we describe three isolates that provide a broader view of the pentose sugar catabolism in the P. putida group. One of these isolates clusters with the well-characterized P. alloputida KT2440 (Strain BP6); the second isolate clustered with plant growth-promoting strain P. putida W619 (Strain M2), while the third isolate represents a new species in the group (Strain BP8). Each of these isolates possessed homologous genes for oxidative xylose catabolism (xylDXA) and a potential xylonate transporter. Strain M2 grew on arabinose and had genes for oxidative arabinose catabolism (araDXA). A CRISPR interference (CRISPRi) system was developed for strain M2 and identified conditionally essential genes for xylose growth. A glucose dehydrogenase was found to be responsible for initial oxidation of xylose and arabinose in strain M2. These isolates have illuminated inherent diversity in pentose catabolism in the P. putida group and may provide alternative hosts for biomass conversion.
Topics: Pentoses; Xylose; Arabinose; Pseudomonas putida; Oxidative Stress
PubMed: 36465038
DOI: 10.1111/1462-2920.16296 -
Scientific Reports Mar 2022Urinary free-glycans are promising markers of disease. In this study, we attempted to identify novel tumor markers by focusing on neutral free-glycans in urine....
Urinary free-glycans are promising markers of disease. In this study, we attempted to identify novel tumor markers by focusing on neutral free-glycans in urine. Free-glycans extracted from the urine of normal subjects and cancer patients with gastric, colorectal, pancreatic and bile duct were fluorescently labeled with 2-aminopyridine. Profiles of these neutral free-glycans constructed using multidimensional high performance liquid chromatography separation were compared between normal controls and cancer patients. The analysis identified one glycan in the urine of cancer patients with a unique structure, which included a pentose residue. To reveal the glycan structure, the linkage fashion, monosaccharide species and enantiomer of the pentose were analyzed by high performance liquid chromatography and mass spectrometry combined with several chemical treatments. The backbone of the glycan was a monoantennary complex-type free-N-glycan containing β1,4-branch. The pentose residue was attached to the antennal GlcNAc and released by α1,3/4-L-fucosidase. Intriguingly, the pentose residue was consistent with D-arabinose. Collectively, this glycan structure was determined to be Galβ1-4(D-Araβ1-3)GlcNAcβ1-4Manα1-3Manβ1-4GlcNAc-PA. Elevation of D-arabinose-containing free-glycans in the urine of cancer patients was confirmed by selected reaction monitoring. This is the first study to unequivocally show the occurrence of a D-arabinose-containing oligosaccharide in human together with its detailed structure.
Topics: Arabinose; Chromatography, High Pressure Liquid; Glycoside Hydrolases; Humans; Neoplasms; Oligosaccharides; Polysaccharides
PubMed: 35318379
DOI: 10.1038/s41598-022-08790-0 -
Communications Biology Nov 2022Bacteria and Eucarya utilize the non-oxidative pentose phosphate pathway to direct the ribose moieties of nucleosides to central carbon metabolism. Many archaea do not...
Bacteria and Eucarya utilize the non-oxidative pentose phosphate pathway to direct the ribose moieties of nucleosides to central carbon metabolism. Many archaea do not possess this pathway, and instead, Thermococcales utilize a pentose bisphosphate pathway involving ribose-1,5-bisphosphate (R15P) isomerase and ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco). Intriguingly, multiple genomes from halophilic archaea seem only to harbor R15P isomerase, and do not harbor Rubisco. In this study, we identify a previously unrecognized nucleoside degradation pathway in halophilic archaea, composed of guanosine phosphorylase, ATP-dependent ribose-1-phosphate kinase, R15P isomerase, RuBP phosphatase, ribulose-1-phosphate aldolase, and glycolaldehyde reductase. The pathway converts the ribose moiety of guanosine to dihydroxyacetone phosphate and ethylene glycol. Although the metabolic route from guanosine to RuBP via R15P is similar to that of the pentose bisphosphate pathway in Thermococcales, the downstream route does not utilize Rubisco and is unique to halophilic archaea.
Topics: Ribulose-Bisphosphate Carboxylase; Ribose; Pentoses; Archaea; Guanosine; Phosphates
PubMed: 36434094
DOI: 10.1038/s42003-022-04247-2 -
Chemical Reviews Oct 2016Biomass has been long exploited as an anthropogenic energy source; however, the 21st century challenges of energy security and climate change are driving resurgence in... (Review)
Review
Biomass has been long exploited as an anthropogenic energy source; however, the 21st century challenges of energy security and climate change are driving resurgence in its utilization both as a renewable alternative to fossil fuels and as a sustainable carbon feedstock for chemicals production. Deconstruction of cellulose and hemicellulose carbohydrate polymers into their constituent C and C sugars, and subsequent heterogeneously catalyzed transformations, offer the promise of unlocking diverse oxygenates such as furfural, 5-hydroxymethylfurfural, xylitol, sorbitol, mannitol, and gluconic acid as biorefinery platform chemicals. Here, we review recent advances in the design and development of catalysts and processes for C-C sugar reforming into chemical intermediates and products, and highlight the challenges of aqueous phase operation and catalyst evaluation, in addition to process considerations such as solvent and reactor selection.
Topics: Acids; Alkalies; Catalysis; Furaldehyde; Gluconates; Hexoses; Isomerism; Oxidation-Reduction; Pentoses; Sugar Alcohols
PubMed: 27680093
DOI: 10.1021/acs.chemrev.6b00311 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Oct 2018One of the requirements for increasing the economic profitability on the large-scale production of second-generation ethanol and other bio-chemicals using lignocellulose... (Review)
Review
One of the requirements for increasing the economic profitability on the large-scale production of second-generation ethanol and other bio-chemicals using lignocellulose biomass as raw materials is efficient hexose and pentose utilization. Saccharomyces cerevisiae, the traditional ethanol producer, is an attractive chassis cell due to its robustness towards harsh environmental conditions and inherent advantages. But S. cerevisiae cannot utilize pentose. The precision construction of suitable strains for second-generation bio-ethanol production has been taken for more than three decades based on the principle of metabolic engineering and synthetic biology. The resulting strains have improved significantly co-fermentation of glucose and xylose. Recently, much attentions have been focused on sugar transport, which is one of the limiting but formerly ignored step for ethanol production from both glucose and xylose, to get the desired state that different sugars could efficiently delivered by their individual specific transporters. In this paper, the progress on sugar transporters of S. cerevisiae was reviewed, and the research status of xylose and/or L-arabinose metabolic engineering in S. cerevisiae were also presented.
Topics: Arabinose; Biological Transport; Biomass; Ethanol; Fermentation; Glucose; Industrial Microbiology; Lignin; Metabolic Engineering; Monosaccharide Transport Proteins; Pentoses; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Xylose
PubMed: 30394022
DOI: 10.13345/j.cjb.180031 -
Scientific Reports Apr 2017We describe an integrated and straightforward new analytical protocol that identifies plant gums from various sample sources including cultural heritage. Our approach is...
We describe an integrated and straightforward new analytical protocol that identifies plant gums from various sample sources including cultural heritage. Our approach is based on the identification of saccharidic fingerprints using mass spectrometry following controlled enzymatic hydrolysis. We developed an enzyme cocktail suitable for plant gums of unknown composition. Distinctive MS profiles of gums such as arabic, cherry and locust-bean gums were successfully identified. A wide range of oligosaccharidic combinations of pentose, hexose, deoxyhexose and hexuronic acid were accurately identified in gum arabic whereas cherry and locust bean gums showed respectively PentHex and Hex profiles. Optimized for low sample quantities, the analytical protocol was successfully applied to contemporary and historic samples including 'Colour Box Charles Roberson &Co' dating 1870s and drawings from the American painter Arthur Dove (1880-1946). This is the first time that a gum is accurately identified in a cultural heritage sample using structural information. Furthermore, this methodology is applicable to other domains (food, cosmetic, pharmaceutical, biomedical).
Topics: Carbohydrate Sequence; Galactans; Gum Arabic; Hexoses; Hexuronic Acids; History, 19th Century; Humans; Mannans; Oligosaccharides; Paintings; Pentoses; Pictorial Works as Topic; Plant Gums; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 28425501
DOI: 10.1038/srep44538