Authors: Erin F Boulanger, Anice Sabag-Daigle, Pankajavalli Thirugnanasambantham...

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

Review

Authors: Yifeng Wei, Yang Tong, Yan Zhang...

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

Authors: Yuta Michimori, Rikihisa Izaki, Yu Su...

Many organisms that utilize the Calvin-Benson-Bassham (CBB) cycle for autotrophic growth harbor metabolic pathways to remove and/or salvage 2-phosphoglycolate, the product of the oxygenase activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). It has been presumed that the occurrence of 2-phosphoglycolate salvage is linked to the CBB cycle, and in particular, the C2 pathway to the CBB cycle and oxygenic photosynthesis. Here, we examined 2-phosphoglycolate salvage in the hyperthermophilic archaeon , an obligate anaerobe that harbors a Rubisco that functions in the pentose bisphosphate pathway. harbors enzymes that have the potential to convert 2-phosphoglycolate to glycine and serine, and their genes were identified by biochemical and/or genetic analyses. 2-phosphoglycolate phosphatase activity increased 1.6-fold when cells were grown under microaerobic conditions compared to anaerobic conditions. Among two candidates, TK1734 encoded a phosphatase specific for 2-phosphoglycolate, and the enzyme was responsible for 80% of the 2-phosphoglycolate phosphatase activity in cells. The TK1734 disruption strain displayed growth impairment under microaerobic conditions, which was relieved upon addition of sodium sulfide. In addition, glycolate was detected in the medium when was grown under microaerobic conditions. The results suggest that removes 2-phosphoglycolate via a phosphatase reaction followed by secretion of glycolate to the medium. As the Rubisco in functions in the pentose bisphosphate pathway and not in the CBB cycle, mechanisms to remove 2-phosphoglycolate in this archaeon emerged independent of the CBB cycle.

Topics: Ribulose-Bisphosphate Carboxylase; Archaea; Photosynthesis; Glycolates; Phosphoric Monoester Hydrolases; Oxygenases; Pentoses

PubMed: 38593075
DOI: 10.1073/pnas.2311390121

Comparative Study Review

Authors: Michaela Falb, Kerstin Müller, Lisa Königsmaier...

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

Review

Authors: Venkatesh Endalur Gopinarayanan, Nikhil U Nair

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

Authors: Clara Granzotto, Julie Arslanoglu, Christian Rolando...

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

Authors: Takaaki Sato, Sanae Hodo Utashima, Yuta Yoshii...

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

Review

Authors: Kler Huonnic, Bruno Linclau

Fluorinated carbohydrates have found many applications in the glycosciences. Typically, these contain fluorination at a single position. There are not many applications involving polyfluorinated carbohydrates, here defined as monosaccharides in which more than one carbon has at least one fluorine substituent directly attached to it, with the notable exception of their use as mechanism-based inhibitors. The increasing attention to carbohydrate physical properties, especially around lipophilicity, has resulted in a surge of interest for this class of compounds. This review covers the considerable body of work toward the synthesis of polyfluorinated hexoses, pentoses, ketosugars, and aminosugars including sialic acids and nucleosides. An overview of the current state of the art of their glycosidation is also provided.

Topics: Fluorine; Carbohydrates; Hexoses; Pentoses; Monosaccharides; Nucleosides; Sialic Acids; Carbon

PubMed: 35613331
DOI: 10.1021/acs.chemrev.2c00086

Review

Authors: Suji Ye, Jeong-Won Kim, Soo Rin Kim...

L-Arabinose, a five carbon sugar, has not been considered as an important bioresource because most studies have focused on D-xylose, another type of five-carbon sugar that is prevalent as a monomeric structure of hemicellulose. In fact, L-arabinose is also an important monomer of hemicellulose, but its content is much more significant in pectin (3-22%, g/g pectin), which is considered an alternative biomass due to its low lignin content and mass production as juiceprocessing waste. This review presents native and engineered microorganisms that can ferment L-arabinose. is highlighted as the most preferred engineering host for expressing a heterologous arabinose pathway for producing ethanol. Because metabolic engineering efforts have been limited so far, with this review as momentum, more attention to research is needed on the fermentation of L-arabinose as well as the utilization of pectin-rich biomass.

Topics: Arabinose; Bacteria; Biomass; Ethanol; Fermentation; Fungi; Lignin; Metabolic Engineering; Metabolic Networks and Pathways; Pectins; Pentoses; Polysaccharides; Saccharomyces cerevisiae; Xylose

PubMed: 30786700
DOI: 10.4014/jmb.1812.12015

Review

Authors: Steven Ochoa, Valeria T Milam

In the last three decades, oligonucleotides have been extensively investigated as probes, molecular ligands and even catalysts within therapeutic and diagnostic applications. The narrow chemical repertoire of natural nucleic acids, however, imposes restrictions on the functional scope of oligonucleotides. Initial efforts to overcome this deficiency in chemical diversity included conservative modifications to the sugar-phosphate backbone or the pendant base groups and resulted in enhanced in vivo performance. More importantly, later work involving other modifications led to the realization of new functional characteristics beyond initial intended therapeutic and diagnostic prospects. These results have inspired the exploration of increasingly exotic chemistries highly divergent from the canonical nucleic acid chemical structure that possess unnatural physiochemical properties. In this review, the authors highlight recent developments in modified oligonucleotides and the thrust towards designing novel nucleic acid-based ligands and catalysts with specifically engineered functions inaccessible to natural oligonucleotides.

Topics: Animals; Aptamers, Nucleotide; Base Pairing; Carbohydrates; Catalysis; Enzymes; Gene Editing; Humans; Ligands; Nucleic Acids; Oligonucleotides; Oligonucleotides, Antisense; Pentoses

PubMed: 33066073
DOI: 10.3390/molecules25204659