Inhibitory Effect of 2-Deoxy-
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            -Glucose on the Formation of the Cell Wall in Yeast Protoplasts

Farkaš, Vladimı́r; Svoboda, Augustín; Bauer, Štefan

doi:10.1128/jb.98.2.744-748.1969

Cited by 45 publications

(16 citation statements)

References 12 publications

(12 reference statements)

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“…The regeneration required at least 2 nutritional elements, Czapek-box's minerals and glucose. Glucose is probably incorporated into new wall materials, because no colonies developed upon the addition of 2-deoxy-D-glucose to the medium as previously reported by others [14,15]. Glucose may also be an energy source.…”

Section: Discussionmentioning

confidence: 51%

Magnesium‐Stimulated Resynthesis of Osmoresistant Layer by Candida albicans Spheroplasts

Ota

1972

Japanese Journal of Microbiology

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Spheroplasts of Candida albicans could be obtained by treating cells with a snail enzyme in the presence of 0.75 M MgSO4 as a stabilizer and cells could subsequently be regenerated by the thin-layer-agar plating method. The initial regeneration process was affected by stabilizers such as MgSO4, MgCl2, A/InSO4, CaCl2, KCl, NaCl and sucrose. It was found that 0.68 m MgSO4 was the best stabilizer. Good stabilization was also achieved in any medium with 0.5-0.75 m sucrose, although stabilizing agents were in general most effective at concentrations giving about 22 atmospheres of osmolarity. This osmolarity was lower than that used to prepare spheroplasts. Using this thin-layer plating method at least three factors were essential for resynthesis of a wall layer: (1) a carbon source, (2) a stabilizer and (3) several minerals. Nitrogen in the form of an amino acid stimulated formation of the wall layer. Relationship between these factors and osmolarity of the medium during regeneration of the wall layer is discussed.

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Section: Discussionmentioning

confidence: 51%

Magnesium‐Stimulated Resynthesis of Osmoresistant Layer by Candida albicans Spheroplasts

Ota

1972

Japanese Journal of Microbiology

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“…However, the latter authors showed that deGlc was not incorporated into the walls of the fission yeast, although incorporation has been demonstrated into wall glucan of Saccharomyces cerevisiae (Biely et al, 1971;Kratky, Biely and Bauer, 1975). Rather than being due to inclusion of the analogue, general weakening of the wall is thought to be largely the consequence of interference by phosphorylated metabolites of deGlc with metabolic processes involved in the incorporation of glucose and mannose into structural wall polysaccharides Farkas, Svoboda et al, 1969;Biely et al, 1971). The phosphorylated metabolites include both uridine and guanosine nucleotide derivatives Bauer, 1966, 1968;Jaspers and van Steveninck, 1976).…”

Section: Mechanisms Of Inhibition : 2-deoxy-d-glucose and Related Sugarsmentioning

confidence: 99%

“…The reduced net accumulation of glycogen may result from acceleration of glycogen breakdown rather than a true inhibition of synthesis (Webb, 1966). Synthesis of glycogen in hepatoma cells is also inhibited by deGlc (Nigam, 1966) and it is 5OO D. MOORE certainly the case that this analogue stimulates degradation of glycogen in yeast (Farkas, Svoboda & Bauer, 1969). In this latter case, though, deGlc was not incorporated into glycogen in vivo despite the facts that an in vitro enzyme system can incorporate deGlc into some outer chains of the glycogen primer (Biely, Farkas and Bauer, 1967) and incorporation into glycogen in vivo had been demonstrated in hepatoma cells (Nigam, 1967).…”

Section: Mechanisms Of Inhibition : 2-deoxy-d-glucose and Related Sugarsmentioning

confidence: 99%

Effects of Hexose Analogues on Fungi: Mechanisms of Ingibition and of Resistance

Moore

1981

New Phytologist

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I. SUMMARY Although the effects of a number of sugar analogues are discussed in this review, most attention is devoted to 2‐deoxy‐D‐glucose (deGlc) and L‐sorbose. The growth of fungi is not uniformly inhibited by sugar analogues since some species or strains can metabolize sugars which severely inhibit others. Sugar analogues usually cause inhibitions by being used in metabolism in place of glucose. Both deGlc and sorbose are metabolized by several species but, in general, only a small fraction of the analogue is utilized. The uptake and phosphorylation of readily metabolized sugars are inhibited by deGlc. Inhibitions by sugar analogues occur on media containing non‐carbohydrate sources of carbon, so inhibition of sugar uptake is unlikely to be a major component of the growth inhibition which occurs on sugar‐containing media. Hexokinase phosphorylates deGlc, and its 6‐phosphate inhibits the activity of especially phosphohexose isomerase and glucose 6‐phosphate dehydrogenase. Apart from an involvement in synthesis of more complex sugars, formation of deGlc‐6P is the usual limit of metabolism of this sugar analogue. Accumulation of the phosphate ester leads to a considerable drain on phosphate pools and ATP levels decline drastically. Indeed, deGlc rapidly initiates degradation of purine nucleotides which can proceed at least to the level of hypoxanthine. In Saccharomyces cerevisiae, deGlc can be condensed to dideoxytrehalose and, in most fungi, polysaccharide synthesis is affected. Preformed wall material is eroded and synthesis of new wall components is prevented by sequestering of uridine and guanosine nucleotides through reaction with deGlc. Interference with the structure of the wall greatly reduces osmotic stability, and cell lysis is the major cause of inhibition of growth by deGlc in yeasts and filamentous fungi alike. L‐Sorbose is not phosphorylated, and the biochemical basis of the inhibitions caused by this analogue is obscure. Some enzymes involved in polysaccharide synthesis are sensitive to inhibition by sorbose, and a characteristic of growth on this sugar is formation of an abnormally thick cell wall. Filamentous fungi grown on solid medium containing sorbose assume an abnormal growth form in which cells are much shortened and branching frequency is increased. There are indications that sorbose, perhaps by interfering with cell wall structure, affects hyphal morphogenesis and that this effect may be magnified into a macroscopic change in the characteristics of the colony during growth on solid medium by secondary environmental effects. Mutants, resistant to deGlc, have alterations in either transport, hexokinase or phosphatase functions, thus emphasizing the important of accumulation of deGlc‐6P in the inhibitions caused by this analogue. Generalization is less easy about mutants resistant to sorbose. The majority are defective in transport, but others show defects in phosphoglucomutase and polysaccharide synthases and there are some correlations with morphological changes which underline the involv...

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“…nidulans. The second compound, 2-deoxyglucose, which inhibits wall synthesis in both young yeast cells (Johnson, 1968) and yeast protoplasts (Farkas et al, 1969) as well as retarding the synthesis of the a-glucan wall component of A. nidulans (Zonneveld, 1973), was found to delay the regeneration of cell walls by protoplasts of A . nidulans for up to 12 h. The third inhibitor tested was a group of closely related uracil nucleotide antibiotics termed polyoxins which are produced together in broth cultures of Streptomyces cacaoi var.…”

Section: R E S U L T Smentioning

confidence: 99%

Co-synthesis of Penicillin Following Treatment of Mutants of Aspergillus nidulans Impaired in Antibiotic Production with Lytic Enzymes

Makins¹,

Holt²,

Macdonald³

1980

Microbiology

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Mycelia from four mutants of Aspergillus nidulans impaired in penicillin production at separate genetic loci were treated with an enzyme complex capable of lysine cell walls, then mixed in all possible paired combinations and grown in osmotically buffered penicillin production media, containing 2-deoxyglucose and an unrefined mixture of polyoxins to prevent cell wall regeneration. The culture filtrates were assayed after 6 d and significant penicillin yields were observed in four of the six possible combinations. None of these pairs produced penicillin when grown together as normal mycelium, suggesting that intermediates of the penicillin biosynthetic pathway unable to diffuse from untreated mycelium could do so from enzyme-treated mycelium when cell wall regeneration was inhibited. A general method is thus available for examining biochemical pathways with mutants accumulating intermediates unable to cross the cell wall barrier.

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Inhibitory Effect of 2-Deoxy- d -Glucose on the Formation of the Cell Wall in Yeast Protoplasts

Cited by 45 publications

References 12 publications

Magnesium‐Stimulated Resynthesis of Osmoresistant Layer by Candida albicans Spheroplasts

Magnesium‐Stimulated Resynthesis of Osmoresistant Layer by Candida albicans Spheroplasts

Effects of Hexose Analogues on Fungi: Mechanisms of Ingibition and of Resistance

Co-synthesis of Penicillin Following Treatment of Mutants of Aspergillus nidulans Impaired in Antibiotic Production with Lytic Enzymes

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