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Carcinogenesis Aug 2023Glucose-6-phosphate dehydrogenase (G6PD) is involved in the catalytic pentose phosphate pathway (PPP), which is closely related to energy metabolism. G6PD plays a...
Glucose-6-phosphate dehydrogenase (G6PD) is involved in the catalytic pentose phosphate pathway (PPP), which is closely related to energy metabolism. G6PD plays a crucial role in many types of cancer, but the specific molecular mechanisms of G6PD in cancer remain unclear. Therefore, we investigated the potential oncogenic role of G6PD in various tumors based on The Cancer Genome Atlas (TCGA), the cBioPortal datasets, the University of California Santa Cruz (UCSC) Xena browser, and the UALCAN-based online tool. G6PD was highly expressed in several cancer tissues (hepatocellular carcinoma, glioma, and breast cancer) compared with normal tissues and was significantly associated with poor prognosis of hepatocellular carcinoma, clear cell renal cell carcinoma, and breast cancer. Promoter methylation levels of G6PD were lower in Bladder Urothelial Carcinoma (BLCA) (P = 2.77e-02), breast invasive carcinoma (BRCA) (P = 1.62e-12), kidney renal clear cell carcinoma (KIRC) (P = 4.23e-02), kidney renal papillary cell carcinoma (KIRP) (P = 2.64e-03), liver hepatocellular carcinoma (LIHC) (P = 1.76e-02), stomach adenocarcinoma (STAD) (P = 3.50e-02), testicular germ cell tumors (TGCT) (P = 1.62e-12), higher in prostate adenocarcinoma (PRAD) (P = 1.81e-09), and uterine corpus endometrial carcinoma (UCEC) (P = 2.96e-04) compared with corresponding normal tissue samples. G6PD expression was positively correlated with the infiltration level of immune cells in most tumors, suggesting that G6PD may be involved in tumor immune infiltration. In addition, the functional mechanism of G6PD also involves 'Carbon metabolism', 'Glycolysis/Gluconeogenesis', 'Pentose phosphate pathway', and 'Central carbon pathway metabolism in cancer signaling pathway'. This pan-cancer study provides a relatively broad understanding of the oncogenic role of G6PD in various tumors and presents a theoretical basis for the development of G6PD inhibitors as therapeutic drugs for multiple cancers.
Topics: Humans; Male; Adenocarcinoma; Breast Neoplasms; Carbon; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Glucosephosphate Dehydrogenase; Kidney Neoplasms; Liver Neoplasms; Pentoses; Phosphates; Urinary Bladder Neoplasms
PubMed: 37335542
DOI: 10.1093/carcin/bgad043 -
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 -
Nature Metabolism May 2023Glucose is vital for life, serving as both a source of energy and carbon building block for growth. When glucose is limiting, alternative nutrients must be harnessed. To...
Glucose is vital for life, serving as both a source of energy and carbon building block for growth. When glucose is limiting, alternative nutrients must be harnessed. To identify mechanisms by which cells can tolerate complete loss of glucose, we performed nutrient-sensitized genome-wide genetic screens and a PRISM growth assay across 482 cancer cell lines. We report that catabolism of uridine from the medium enables the growth of cells in the complete absence of glucose. While previous studies have shown that uridine can be salvaged to support pyrimidine synthesis in the setting of mitochondrial oxidative phosphorylation deficiency, our work demonstrates that the ribose moiety of uridine or RNA can be salvaged to fulfil energy requirements via a pathway based on: (1) the phosphorylytic cleavage of uridine by uridine phosphorylase UPP1/UPP2 into uracil and ribose-1-phosphate (R1P), (2) the conversion of uridine-derived R1P into fructose-6-P and glyceraldehyde-3-P by the non-oxidative branch of the pentose phosphate pathway and (3) their glycolytic utilization to fuel ATP production, biosynthesis and gluconeogenesis. Capacity for glycolysis from uridine-derived ribose appears widespread, and we confirm its activity in cancer lineages, primary macrophages and mice in vivo. An interesting property of this pathway is that R1P enters downstream of the initial, highly regulated steps of glucose transport and upper glycolysis. We anticipate that 'uridine bypass' of upper glycolysis could be important in the context of disease and even exploited for therapeutic purposes.
Topics: Ribose; Uridine; RNA; Glycolysis; Humans; Cell Line, Tumor; Oxidative Phosphorylation; Culture Media; Glucose; K562 Cells; Cell Proliferation; Pentose Phosphate Pathway
PubMed: 37198474
DOI: 10.1038/s42255-023-00774-2 -
Applied Microbiology and Biotechnology Feb 2022Xylitol is pentahydroxy sugar alcohol, existing in very trace amount in fruits and vegetables, and finds varied application in industries like food, pharmaceuticals,... (Review)
Review
Xylitol is pentahydroxy sugar alcohol, existing in very trace amount in fruits and vegetables, and finds varied application in industries like food, pharmaceuticals, confectionaries, etc. and is of prime importance to health. Owing to its trace occurrence in nature and considerable increase in market demand that exceeds availability, alternate production through biotechnological and chemical approach is in process. Biochemical production involves substrates like lignocellulosic biomasses and industrial effluents and is an eco-friendly process with high dependency on physico-chemical parameters. Although the chemical processes are faster, high yielding and economical, they have a great limitation as usage of toxic chemicals and thus need to be regulated and replaced by an environment friendly approach. Microbes play a major role in xylitol production through a biotechnological process towards the development of a sustainable system. Major microbes working on assimilation of xylose for production of xylitol include Candida tropicalis, Candida maltose, Bacillus subtilis, Debaromyces hansenii, etc. The present review reports all probable microbial xylitol production biochemical pathways encompassing diverse bioprocesses involved in uptake and conversion of xylose sugars from agricultural residues and industrial effluents. A comprehensive report on xylitol occurrence and biotechnological production processes with varied substrates has been encompassed. KEY POINTS: • Xylitol from agro-industrial waste • Microbial xylose assimilation.
Topics: Biotechnology; Candida tropicalis; Fermentation; Sugar Alcohols; Xylitol; Xylose
PubMed: 35089402
DOI: 10.1007/s00253-022-11793-6 -
FEMS Microbiology Reviews Aug 2021Pentose sugars are widespread in nature and two of them, D-xylose and L-arabinose belong to the most abundant sugars being the second and third by abundance sugars in... (Review)
Review
Pentose sugars are widespread in nature and two of them, D-xylose and L-arabinose belong to the most abundant sugars being the second and third by abundance sugars in dry plant biomass (lignocellulose) and in general on planet. Therefore, it is not surprising that metabolism and bioconversion of these pentoses attract much attention. Several different pathways of D-xylose and L-arabinose catabolism in bacteria and yeasts are known. There are even more common and really ubiquitous though not so abundant pentoses, D-ribose and 2-deoxy-D-ribose, the constituents of all living cells. Thus, ribose metabolism is example of endogenous metabolism whereas metabolism of other pentoses, including xylose and L-arabinose, represents examples of the metabolism of foreign exogenous compounds which normally are not constituents of yeast cells. As a rule, pentose degradation by the wild-type strains of microorganisms does not lead to accumulation of high amounts of valuable substances; however, productive strains have been obtained by random selection and metabolic engineering. There are numerous reviews on xylose and (less) L-arabinose metabolism and conversion to high value substances; however, they mostly are devoted to bacteria or the yeast Saccharomyces cerevisiae. This review is devoted to reviewing pentose metabolism and bioconversion mostly in non-conventional yeasts, which naturally metabolize xylose. Pentose metabolism in the recombinant strains of S. cerevisiae is also considered for comparison. The available data on ribose, xylose, L-arabinose transport, metabolism, regulation of these processes, interaction with glucose catabolism and construction of the productive strains of high-value chemicals or pentose (ribose) itself are described. In addition, genome studies of the natural xylose metabolizing yeasts and available tools for their molecular research are reviewed. Metabolism of other pentoses (2-deoxyribose, D-arabinose, lyxose) is briefly reviewed.
Topics: Arabinose; Biofuels; Pentoses; Saccharomyces cerevisiae; Xylose
PubMed: 33316044
DOI: 10.1093/femsre/fuaa069 -
Current Opinion in Biotechnology Feb 2021Biosynthesis of oleochemicals enables sustainable production of natural and unnatural alternatives from renewable feedstocks. Yeast cell factories have been extensively... (Review)
Review
Biosynthesis of oleochemicals enables sustainable production of natural and unnatural alternatives from renewable feedstocks. Yeast cell factories have been extensively studied and engineered to produce a variety of oleochemicals, focusing on both central carbon metabolism and lipid metabolism. Here, we review recent progress towards oleochemical synthesis in yeast based biorefineries, as well as utilization of alternative renewable feedstocks, such as xylose and l-arabinose. We also review recent studies of C1 compound utilization or co-utilization and discuss how these studies can lead to third generation yeast based biorefineries for oleochemical production.
Topics: Carbon; Saccharomyces cerevisiae; Xylose
PubMed: 33360103
DOI: 10.1016/j.copbio.2020.11.009 -
Bioscience Reports Oct 2022Sulfoquinovose (SQ, 6-deoxy-6-sulfo-D-glucose) is a sulfo-sugar with a ubiquitous distribution in the environment due to its production by plants and other... (Review)
Review
Sulfoquinovose (SQ, 6-deoxy-6-sulfo-D-glucose) is a sulfo-sugar with a ubiquitous distribution in the environment due to its production by plants and other photosynthetic organisms. Bacteria play an important role in degradation of SQ and recycling of its constituent sulfur and carbon. Since its discovery in 1963, SQ was noted to have a structural resemblance to glucose-6-phosphate and proposed to be degraded through a pathway analogous to glycolysis, termed sulfoglycolysis. Studies in recent years have uncovered an unexpectedly diverse array of sulfoglycolytic pathways in different bacteria, including one analogous to the Embden-Meyerhof-Parnas pathway (sulfo-EMP), one analogous to the Entner-Doudoroff pathway (sulfo-ED), and two involving sulfo-sugar cleavage by a transaldolase (sulfo-TAL) and transketolase (sulfo-TK), respectively, analogous to reactions in the pentose phosphate (PP) pathway. In addition, a non-sulfoglycolytic SQ degradation pathway was also reported, involving oxygenolytic C-S cleavage catalyzed by a homolog of alkanesulfonate monooxygenase (sulfo-ASMO). Here, we review the discovery of these new mechanisms of SQ degradation and lessons learnt in the study of new catabolic enzymes and pathways in bacteria.
Topics: Transaldolase; Glucose-6-Phosphate; Transketolase; Bacteria; Glycolysis; Sulfur; Glucose; Carbon; Alkanesulfonates; Mixed Function Oxygenases; Phosphates; Pentoses
PubMed: 36196895
DOI: 10.1042/BSR20220314 -
Nature Communications Nov 2023Tankyrase 1 and 2 are ADP-ribosyltransferases that catalyze formation of polyADP-Ribose (PAR) onto themselves and their binding partners. Tankyrase protein levels are...
Tankyrase 1 and 2 are ADP-ribosyltransferases that catalyze formation of polyADP-Ribose (PAR) onto themselves and their binding partners. Tankyrase protein levels are regulated by the PAR-binding E3 ligase RNF146, which promotes K48-linked polyubiquitylation and proteasomal degradation of tankyrase and its partners. We identified a novel interaction between tankyrase and a distinct class of E3 ligases: the RING-UIM (Ubiquitin-Interacting Motif) family. We show that RNF114 and RNF166 bind and stabilize monoubiquitylated tankyrase and promote K11-linked diubiquitylation. This action competes with RNF146-mediated degradation, leading to stabilization of tankyrase and its binding partner, Angiomotin, a cancer cell signaling protein. Moreover, we identify multiple PAR-binding E3 ligases that promote ubiquitylation of tankyrase and induce stabilization or degradation. Discovery of K11 ubiquitylation that opposes degradation, along with identification of multiple PAR-binding E3 ligases that ubiquitylate tankyrase, provide insights into mechanisms of tankyrase regulation and may offer additional uses for tankyrase inhibitors in cancer therapy.
Topics: Ubiquitin-Protein Ligases; Tankyrases; Ubiquitination; ADP Ribose Transferases; Catalysis; Ribose
PubMed: 37938264
DOI: 10.1038/s41467-023-42939-3 -
Journal of Agricultural and Food... May 2023The complete degradation of abundant xylan derived from plants requires the participation of β-xylosidases to produce the xylose which can be converted to xylitol,... (Review)
Review
The complete degradation of abundant xylan derived from plants requires the participation of β-xylosidases to produce the xylose which can be converted to xylitol, ethanol, and other valuable chemicals. Some phytochemicals can also be hydrolyzed by β-xylosidases into bioactive substances, such as ginsenosides, 10-deacetyltaxol, cycloastragenol, and anthocyanidins. On the contrary, some hydroxyl-containing substances such as alcohols, sugars, and phenols can be xylosylated by β-xylosidases into new chemicals such as alkyl xylosides, oligosaccharides, and xylosylated phenols. Thus, β-xylosidases shows great application prospects in food, brewing, and pharmaceutical industries. This review focuses on the molecular structures, biochemical properties, and bioactive substance transformation function of β-xylosidases derived from bacteria, fungi, actinomycetes, and metagenomes. The molecular mechanisms of β-xylosidases related to the properties and functions are also discussed. This review will serve as a reference for the engineering and application of β-xylosidases in food, brewing, and pharmaceutical industries.
Topics: Xylosidases; Oligosaccharides; Xylose; Fungi
PubMed: 37192316
DOI: 10.1021/acs.jafc.3c01425 -
Biotechnology Advances 2023The conventional yeast (Saccharomyces cerevisiae) is the most studied yeast and has been used in many important industrial productions, especially in bioethanol... (Review)
Review
The conventional yeast (Saccharomyces cerevisiae) is the most studied yeast and has been used in many important industrial productions, especially in bioethanol production from first generation feedstock (sugar and starchy biomass). However, for reduced cost and to avoid competition with food, second generation bioethanol, which is produced from lignocellulosic feedstock, is now being investigated. Production of second generation bioethanol involves pre-treatment and hydrolysis of lignocellulosic biomass to sugar monomers containing, amongst others, d-glucose and D-xylose. Intrinsically, S. cerevisiae strains lack the ability to ferment pentose sugars and genetic engineering of S. cerevisiae to inculcate the ability to ferment pentose sugars is ongoing to develop recombinant strains with the required stability and robustness for commercial second generation bioethanol production. Furthermore, pre-treatment of these lignocellulosic wastes leads to the release of inhibitory compounds which adversely affect the growth and fermentation by S. cerevisae. S. cerevisiae also lacks the ability to grow at high temperatures which favour Simultaneous Saccharification and Fermentation of substrates to bioethanol. There is, therefore, a need for robust yeast species which can co-ferment hexose and pentose sugars and can tolerate high temperatures and the inhibitory substances produced during pre-treatment and hydrolysis of lignocellulosic materials. Non-conventional yeast strains are potential solutions to these problems due to their abilities to ferment both hexose and pentose sugars, and tolerate high temperature and stress conditions encountered during ethanol production from lignocellulosic hydrolysate. This review highlights the limitations of the conventional yeast species and the potentials of non-conventional yeast strains in commercialization of second generation bioethanol.
Topics: Saccharomyces cerevisiae; Pentoses; Xylose; Genetic Engineering; Fermentation
PubMed: 36669745
DOI: 10.1016/j.biotechadv.2023.108100