Synthesis, trehalase hydrolytic resistance and inhibition properties of 4- and 6-substituted trehalose derivatives

Dhaene, Shari; Eycken, Johan Van der; Beerens, Koen; Franceus, Jorick; Desmet, Tom; Caroen, Jurgen

doi:10.1080/14756366.2020.1837125

Cited by 8 publications

(3 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2014 ). Similarly, trehalose derivates, such as validamycin A (R = β-D-glucopyranosyl) and validamycin A (R = H) have shown a half maximal inhibitory concentration of 1.8 × 10 −3 mM and 1.1 × 10 −5 mM, respectively, towards Mycobacterium smegmatis trehalase ( Dhaene et al. 2020 ).…”

Section: Application Of Trehalose-degrading Enzymes and Their Future ...mentioning

confidence: 99%

Elucidation of bacterial trehalose-degrading trehalase and trehalose phosphorylase: physiological significance and its potential applications

Shrestha,

Karmacharya,

Han

et al. 2023

Glycobiology

View full text Add to dashboard Cite

Bacteria possess diverse metabolic and genetic processes, resulting in the inability of certain bacteria to degrade trehalose. However, some bacteria do have the capability to degrade trehalose, utilizing it as a carbon source, and for defense against environmental stress. Trehalose, a disaccharide, serves as a carbon source for many bacteria, including some that are vital for pathogens. The degradation of trehalose is carried out by enzymes like trehalase (EC 3.2.1.28) and trehalose phosphorylase (EC 2.4.1.64/2.4.1.231), which are classified under the glycoside hydrolase families GH37, GH15, and GH65. Numerous studies and reports have explored the physiological functions, recombinant expression, enzymatic characteristics, and potential applications of these enzymes. However, further research is still being conducted to understand their roles in bacteria. This review aims to provide a comprehensive summary of the current understanding of trehalose degradation pathways in various bacteria, focusing on three key areas: (i) identifying different trehalose-degrading enzymes in Gram-positive and Gram-negative bacteria, (ii) elucidating the mechanisms employed by trehalose-degrading enzymes belonging to the glycoside hydrolases GH37, GH15, and GH65, and (iii) discussing the potential applications of these enzymes in different sectors. Notably, this review emphasizes the bacterial trehalose-degrading enzymes, specifically trehalases (GH37, GH15, and GH65) and trehalose phosphorylases (GH65), in both Gram-positive and Gram-negative bacteria, an aspect that has not been highlighted before.

show abstract

Section: Application Of Trehalose-degrading Enzymes and Their Future ...mentioning

confidence: 99%

Elucidation of bacterial trehalose-degrading trehalase and trehalose phosphorylase: physiological significance and its potential applications

Shrestha,

Karmacharya,

Han

et al. 2023

Glycobiology

View full text Add to dashboard Cite

show abstract

“…The human trehalase, present in the kidney, small intestine, and liver, has been used to detect patients with kidney and liver disorders by measuring urinary and serum trehalase (Ishihara et al, 1997). Some studies on inhibiting this enzyme based on substrate analog pseudo‐disaccharide compounds have already demonstrated the effectiveness of attacking this biochemical function (Dhaene et al, 2020). Among them, validamycin A is an antibiotic and fungicide produced by Streptomyces hygroscopicus , and the first trehalase inhibitor commercialized since the late 1960s (Yu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Toxicological, biochemical, and in silico investigations of three trehalase inhibitors for new ways to control aphids

Neyman,

Quicray,

Francis

et al. 2024

Arch Insect Biochem Physiol

View full text Add to dashboard Cite

Insect trehalases have been identified as promising new targets for pest control. These key enzymes are involved in trehalose hydrolysis and plays an important role in insect growth and development. In this contribution, plant and microbial compounds, namely validamycin A, amygdalin, and phloridzin, were evaluated for their effect, through trehalase inhibition, on Acyrthosiphon pisum aphid. The latter is part of the Aphididae family, main pests as phytovirus vectors and being very harmful for crops. Validamycin A was confirmed as an excellent trehalase inhibitor with an half maximal inhibitory concentration and inhibitor constant of 2.2 × 10−7 and 5 × 10−8 M, respectively, with a mortality rate of ~80% on a A. pisum population. Unlike validamycin A, the insect lethal efficacy of amygdalin and phloridzin did not correspond to their trehalase inhibition, probably due to their hydrolysis by insect β‐glucosidases. Our docking studies showed that none of the three compounds can bind to the trehalase active site, unlike their hydrolyzed counterparts, that is, validoxylamine A, phloretin, and prunasin. Validoxylamine A would be by far the best trehalase binder, followed by phloretin and prunasin.

show abstract

“…Nevertheless, trehalase was also found in the brain of mice [ 2 ] and in the gastrointestinal tract of mice and humans [ 4 ], likely originating in part from the gut microbiome [ 5 , 6 , 7 ]. The bioavailability of ingested trehalose is low [ 8 , 9 ] and may depend on bacteria colonization [ 10 ]. Nevertheless, trehalose-based diets in mice have positive cardiometabolic [ 4 , 11 , 12 ], neuroprotective [ 13 ], and anti-inflammatory properties [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Trehalose Reduces Nerve Injury Induced Nociception in Mice but Negatively Affects Alertness

et al. 2021

View full text Add to dashboard Cite

Trehalose, a sugar from fungi, mimics starvation due to a block of glucose transport and induces Transcription Factor EB- mediated autophagy, likely supported by the upregulation of progranulin. The pro-autophagy effects help to remove pathological proteins and thereby prevent neurodegenerative diseases such as Alzheimer’s disease. Enhancing autophagy also contributes to the resolution of neuropathic pain in mice. Therefore, we here assessed the effects of continuous trehalose administration via drinking water using the mouse Spared Nerve Injury model of neuropathic pain. Trehalose had no effect on drinking, feeding, voluntary wheel running, motor coordination, locomotion, and open field, elevated plus maze, and Barnes Maze behavior, showing that it was well tolerated. However, trehalose reduced nerve injury-evoked nociceptive mechanical and thermal hypersensitivity as compared to vehicle. Trehalose had no effect on calcium currents in primary somatosensory neurons, pointing to central mechanisms of the antinociceptive effects. In IntelliCages, trehalose-treated mice showed reduced activity, in particular, a low frequency of nosepokes, which was associated with a reduced proportion of correct trials and flat learning curves in place preference learning tasks. Mice failed to switch corner preferences and stuck to spontaneously preferred corners. The behavior in IntelliCages is suggestive of sedative effects as a “side effect” of a continuous protracted trehalose treatment, leading to impairment of learning flexibility. Hence, trehalose diet supplements might reduce chronic pain but likely at the expense of alertness.

show abstract

Synthesis, trehalase hydrolytic resistance and inhibition properties of 4- and 6-substituted trehalose derivatives

Cited by 8 publications

References 35 publications

Elucidation of bacterial trehalose-degrading trehalase and trehalose phosphorylase: physiological significance and its potential applications

Elucidation of bacterial trehalose-degrading trehalase and trehalose phosphorylase: physiological significance and its potential applications

Toxicological, biochemical, and in silico investigations of three trehalase inhibitors for new ways to control aphids

Trehalose Reduces Nerve Injury Induced Nociception in Mice but Negatively Affects Alertness

Contact Info

Product

Resources

About