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Molecular Biology Reports Jan 2024D-ribose, an ubiquitous pentose compound found in all living cells, serves as a vital constituent of numerous essential biomolecules, including RNA, nucleotides, and... (Review)
Review
D-ribose, an ubiquitous pentose compound found in all living cells, serves as a vital constituent of numerous essential biomolecules, including RNA, nucleotides, and riboflavin. It plays a crucial role in various fundamental life processes. Within the cellular milieu, exogenously supplied D-ribose can undergo phosphorylation to yield ribose-5-phosphate (R-5-P). This R-5-P compound serves a dual purpose: it not only contributes to adenosine triphosphate (ATP) production through the nonoxidative phase of the pentose phosphate pathway (PPP) but also participates in nucleotide synthesis. Consequently, D-ribose is employed both as a therapeutic agent for enhancing cardiac function in heart failure patients and as a remedy for post-exercise fatigue. Nevertheless, recent clinical studies have suggested a potential link between D-ribose metabolic disturbances and type 2 diabetes mellitus (T2DM) along with its associated complications. Additionally, certain in vitro experiments have indicated that exogenous D-ribose exposure could trigger apoptosis in specific cell lines. This article comprehensively reviews the current advancements in D-ribose's digestion, absorption, transmembrane transport, intracellular metabolic pathways, impact on cellular behaviour, and elevated levels in diabetes mellitus. It also identifies areas requiring further investigation.
Topics: Humans; Diabetes Mellitus, Type 2; Ribose; Heart Failure; Metabolic Diseases; Adenosine Triphosphate
PubMed: 38281218
DOI: 10.1007/s11033-023-09076-y -
Cell Chemical Biology Nov 2023Stimulator of interferon genes (STING) agonists are promising candidates for vaccine adjuvants and antitumor immune stimulants. The most potent natural agonist of STING,...
Stimulator of interferon genes (STING) agonists are promising candidates for vaccine adjuvants and antitumor immune stimulants. The most potent natural agonist of STING, 2',3'-cyclic GMP-AMP (2',3'-cGAMP), is subject to nuclease-mediated inherent metabolic instability, thereby placing limits on its clinical efficacy. Here, we report on a new class of chemically synthesized sugar-modified analogs of 2',3'-cGAMP containing arabinose and xylose sugar derivatives that bind mouse and human STING alleles with high affinity. The co-crystal structures demonstrate that such analogs act as 2',3'-cGAMP mimetics that induce the "closed" conformation of human STING. These analogs show significant resistance to hydrolysis mediated by ENPP1 and increased stability in human serum, while retaining similar potency as 2',3'-cGAMP at inducing IFN-β secretion from human THP1 cells. The arabinose- and xylose-modified 2',3'-cGAMP analogs open a new strategy for overcoming the inherent nuclease-mediated vulnerability of natural ribose cyclic nucleotides, with the additional benefit of high translational potential as cancer therapeutics and vaccine adjuvants.
Topics: Humans; Animals; Mice; Arabinose; Xylose; Adjuvants, Vaccine; Nucleotides, Cyclic
PubMed: 37536341
DOI: 10.1016/j.chembiol.2023.07.002 -
ACS Applied Materials & Interfaces Feb 2023Herein, we report bioderived cross-linkers to create biopolymer-based hydrogels with tunable properties. Nucleosides (inosine and uridine) and ribose (pentose sugar...
Herein, we report bioderived cross-linkers to create biopolymer-based hydrogels with tunable properties. Nucleosides (inosine and uridine) and ribose (pentose sugar lucking the nitrogenous base) were partially oxidized to yield inosine dialdehyde (IdA), uridine dialdehyde (UdA), and ribose dialdehyde (RdA). The dialdehydes were further used as cross-linkers with polysaccharide chitosan to form hydrogels. Depending on the cross-linker type and concentration, the hydrogels showed tunable rheological, mechanical, and liquid holding properties allowing the preparation of injectable, soft, and moldable hydrogels. Computational modeling and molecular dynamics simulations shed light on hydrogel formation and revealed that, in addition to covalent bonding, noncovalent interactions (π-π stacking, cation-π, and H-bonding) also significantly contributed to the cross-linking process. To demonstrate various application possibilities, the prepared hydrogels were used as a growth platform for plant cells, as injectable inks for layer-by-layer 3D printing applications, and as moldable hydrogels for soft lithography to replicate the microstructure of the plant. These findings suggest that the obtained tunable biocompatible hydrogels have the potential to be good candidates for various biotechnological applications.
Topics: Nucleosides; Biocompatible Materials; Hydrogels; Ribose; Chitosan; Uridine
PubMed: 36701767
DOI: 10.1021/acsami.2c19525 -
FEMS Yeast Research Feb 2020Conversion of lignocellulosic biomass to biofuels using microbial fermentation is an attractive option to substitute petroleum-based production economically and... (Review)
Review
Conversion of lignocellulosic biomass to biofuels using microbial fermentation is an attractive option to substitute petroleum-based production economically and sustainably. The substantial efforts to design yeast strains for biomass hydrolysis have led to industrially applicable biological routes. Saccharomyces cerevisiae is a robust microbial platform widely used in biofuel production, based on its amenability to systems and synthetic biology tools. The critical challenges for the efficient microbial conversion of lignocellulosic biomass by engineered S. cerevisiae include heterologous expression of cellulolytic enzymes, co-fermentation of hexose and pentose sugars, and robustness against various stresses. Scientists developed many engineering strategies for cellulolytic S. cerevisiae strains, bringing the application of consolidated bioprocess at an industrial scale. Recent advances in the development and implementation of engineered yeast strains capable of assimilating lignocellulose will be reviewed.
Topics: Biofuels; Cellulose; Fermentation; Hexoses; Hydrolysis; Industrial Microbiology; Lignin; Metabolic Engineering; Pentoses; Saccharomyces cerevisiae
PubMed: 31917414
DOI: 10.1093/femsyr/foz089 -
Organic & Biomolecular Chemistry Sep 2022The search for broad-spectrum antiviral compounds is a continuous mandatory effort. The recent approval of the first -nucleoside carrying a nitrile as a substituent at...
The search for broad-spectrum antiviral compounds is a continuous mandatory effort. The recent approval of the first -nucleoside carrying a nitrile as a substituent at the C1' position of the ribose ring has raised interest in this underexplored substitution pattern. We have previously reported the development of different 1,2,3-triazolyl--ribonucleosides with anticancer and antiviral activities. Herein we report our results on the incorporation of a C1'-CN group in 1,2,3-triazolyl--ribonucleosides.
Topics: Antiviral Agents; Nitriles; Nucleosides; Ribonucleosides; Ribose
PubMed: 36069280
DOI: 10.1039/d2ob01403c -
Organic Letters Jun 2022A general methodology allowing the preparation of phosphonylated 1-spirocyclopropyl analogues of glycosyl-1-phosphates is reported. The scope of this reaction has been...
A general methodology allowing the preparation of phosphonylated 1-spirocyclopropyl analogues of glycosyl-1-phosphates is reported. The scope of this reaction has been assessed using various -glycals easily obtained from the corresponding pyranoses and furanoses. The cyclopropanation was found to be stereospecific, and the selectivity only depends on the / configuration of the starting -glycal. The four possible isomers of spirocyclopropyl ribose-1-phosphonate could thus be prepared in a controlled manner, protected and deprotected.
Topics: Organophosphates; Phosphates; Ribose
PubMed: 35666228
DOI: 10.1021/acs.orglett.2c01422 -
World Journal of Microbiology &... Jun 2022Interest in the production of renewable chemicals from biomass has increased in the past years. Among these chemicals, carboxylic acids represent a significant part of... (Review)
Review
Interest in the production of renewable chemicals from biomass has increased in the past years. Among these chemicals, carboxylic acids represent a significant part of the most desirable bio-based products. Xylonic acid is a five-carbon sugar-acid obtained from xylose oxidation that can be used in several industrial applications, including food, pharmaceutical, and construction industries. So far, the production of xylonic acid has not yet been available at an industrial scale; however, several microbial bio-based production processes are under development. This review summarizes the recent advances in pathway characterization, genetic engineering, and fermentative strategies to improve xylonic acid production by microorganisms from xylose or lignocellulosic hydrolysates. In addition, the strengths of the available microbial strains and processes and the major requirements for achieving biotechnological production of xylonic acid at a commercial scale are discussed. Efficient native and engineered microbial strains have been reported. Xylonic acid titers as high as 586 and 171 g L were obtained from bacterial and yeast strains, respectively, in a laboratory medium. Furthermore, relevant academic and industrial players associated with xylonic acid production will be presented.
Topics: Biomass; Biotechnology; Fermentation; Metabolic Engineering; Xylose
PubMed: 35668329
DOI: 10.1007/s11274-022-03313-5 -
International Journal of Molecular... Apr 2021At the focus of abiotic chemical reactions is the synthesis of ribose. No satisfactory explanation was provided as to the missing link between the prebiotic synthesis of... (Review)
Review
At the focus of abiotic chemical reactions is the synthesis of ribose. No satisfactory explanation was provided as to the missing link between the prebiotic synthesis of ribose and prebiotic RNA (preRNA). Hydrogen cyanide (HCN) is assumed to have been the principal precursor in the prebiotic formation of aldopentoses in the formose reaction and in the synthesis of ribose. Ribose as the best fitting aldopentose became the exclusive sugar component of RNA. The elevated yield of ribose synthesis at higher temperatures and its protection from decomposition could have driven the polymerization of the ribose-phosphate backbone and the coupling of nucleobases to the backbone. RNA could have come into being without the involvement of nucleotide precursors. The first nucleoside monophosphate is likely to have appeared upon the hydrolysis of preRNA contributed by the presence of reactive 2'-OH moieties in the preRNA chain. As a result of phosphorylation, nucleoside monophosphates became nucleoside triphosphates, substrates for the selective synthesis of genRNA.
Topics: Metabolic Networks and Pathways; Nucleotides; Phosphorylation; Polymerization; Purines; Pyrimidines; RNA; Ribose
PubMed: 33917807
DOI: 10.3390/ijms22083857 -
Methods in Enzymology 2023Methylthio-d-ribose-1-phosphate (MTR1P) isomerase (MtnA) catalyzes the reversible isomerization of the aldose MTR1P into the ketose methylthio-d-ribulose 1-phosphate. It...
Methylthio-d-ribose-1-phosphate (MTR1P) isomerase (MtnA) catalyzes the reversible isomerization of the aldose MTR1P into the ketose methylthio-d-ribulose 1-phosphate. It serves as a member of the methionine salvage pathway that many organisms require for recycling methylthio-d-adenosine, a byproduct of S-adenosylmethionine metabolism, back to methionine. MtnA is of mechanistic interest because unlike most other aldose-ketose isomerases, its substrate exists as an anomeric phosphate ester and therefore cannot equilibrate with a ring-opened aldehyde that is otherwise required to promote isomerization. To investigate the mechanism of MtnA, it is necessary to establish reliable methods for determining the concentration of MTR1P and to measure enzyme activity in a continuous assay. This chapter describes several such protocols needed to perform steady-state kinetics measurements. It additionally outlines the preparation of [P]MTR1P, its use in radioactively labeling the enzyme, and the characterization of the resulting phosphoryl adduct.
Topics: Ribose; Kinetics; Aldose-Ketose Isomerases
PubMed: 37245905
DOI: 10.1016/bs.mie.2023.03.015 -
Biomolecules May 2021The pentose phosphate pathway (PPP) is a route that can work in parallel to glycolysis in glucose degradation in most living cells. It has a unidirectional oxidative... (Review)
Review
The pentose phosphate pathway (PPP) is a route that can work in parallel to glycolysis in glucose degradation in most living cells. It has a unidirectional oxidative part with glucose-6-phosphate dehydrogenase as a key enzyme generating NADPH, and a non-oxidative part involving the reversible transketolase and transaldolase reactions, which interchange PPP metabolites with glycolysis. While the oxidative branch is vital to cope with oxidative stress, the non-oxidative branch provides precursors for the synthesis of nucleic, fatty and aromatic amino acids. For glucose catabolism in the baker's yeast , where its components were first discovered and extensively studied, the PPP plays only a minor role. In contrast, PPP and glycolysis contribute almost equally to glucose degradation in other yeasts. We here summarize the data available for the PPP enzymes focusing on and , and describe the phenotypes of gene deletions and the benefits of their overproduction and modification. Reference to other yeasts and to the importance of the PPP in their biotechnological and medical applications is briefly being included. We propose future studies on the PPP in to be of special interest for basic science and as a host for the expression of human disease genes.
Topics: Animals; Glucose; Glycolysis; Humans; Kluyveromyces; Oxidation-Reduction; Oxidative Stress; Pentose Phosphate Pathway; Saccharomyces cerevisiae; Xylose
PubMed: 34065948
DOI: 10.3390/biom11050725