Enzymatic synthesis of a galactose-containing trehalose analogue disaccharide by Pyrococcus horikoshii trehalose-synthesizing glycosyltransferase: Inhibitory effects on several disaccharidase activities

Kim, Hye Min; Chang, You Kyung; Ryu, Soo In; Moon, Sung Gweon; Lee, Soo Bok

doi:10.1016/j.molcatb.2007.08.012

Cited by 24 publications

(18 citation statements)

References 21 publications

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“…26 MurB, the glycosyltransferase that forms the glycosidic linkage for bacterial cell wall biosynthesis, shows significant change in the relative orientation of its two domains, adopting a more closed conformation in the presence of the substrate UDPGlcNAc. 25 For TPS, the loop region (residues [9][10][11][12][13][14][15][16][17][18][19][20][21][22] in the N-terminus makes extensive interactions to the substrate ligand to function as a gate for opening and closing at the front face. 28 However, TreT lacks the corresponding loop region in the active site.…”

Section: Discussionmentioning

confidence: 99%

“…The synthesis and disaccharidase-inhibitory action of the galactose-containing trehalose analog have been previously reported. 20 By the way, TreT from T. tenax is unidirectional and catalyzes only the formation of trehalose, being different from the other reversible TreTs and showing preference for UDPG as the donor substrate. 14 In this study, we present the crystal structure of TreT from P. horikoshii with a binary complex structure of UDP nucleotide in a putative inactive mutant of E326A enzyme.…”

Section: Introductionmentioning

confidence: 97%

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Structural Insights on the New Mechanism of Trehalose Synthesis by Trehalose Synthase TreT from Pyrococcus horikoshii

Woo

Ryu

Song

et al. 2010

Journal of Molecular Biology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Structural Insights on the New Mechanism of Trehalose Synthesis by Trehalose Synthase TreT from Pyrococcus horikoshii

Woo

Ryu

Song

et al. 2010

Journal of Molecular Biology

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“…Early studies by the Lee group on the thermostable TreTs from Thermotoga maritima and Pyrococcus horikoshii indicated moderate to good activity on a few naturally occurring monosaccharides, such as galactose and mannose. 78–80 Furthermore, the trehalose stereoisomer galactotrehalose—discussed later due to its trehalase-resistance property—was synthesized on a semi-preparative scale in 10% isolated yield (based on the acceptor galactose) and characterized by 13 C NMR. 80 These preliminary studies encouraged further research on the TreT pathway for trehalose analogue synthesis.…”

Section: Approaches To Trehalose Analogue Synthesismentioning

confidence: 99%

“…Galactotrehalose (α-D-glucopyranosyl-α-D galactopyranoside, 23 ), a trehalose analogue where one glucose is replaced by galactose, acts as a competitive inhibitor of trehalase. 80 It inhibits trehalase in the high micromolar/low millimolar range. More importantly, mammalian trehalase is unable to degrade galactotrehalose, making it a prime candidate for applications that benefit from resistance to degradation.…”

Section: Applications Of Trehalose Analoguesmentioning

confidence: 99%

Tailoring trehalose for biomedical and biotechnological applications

O'Neill

Piligian

Olson

et al. 2017

Pure and Applied Chemistry

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Trehalose is a non-reducing sugar whose ability to stabilize biomolecules has brought about its widespread use in biological preservation applications. Trehalose is also an essential metabolite in a number of pathogens, most significantly the global pathogen Mycobacterium tuberculosis, though it is absent in humans and other mammals. Recently, there has been a surge of interest in modifying the structure of trehalose to generate analogues that have applications in biomedical research and biotechnology. Non-degradable trehalose analogues could have a number of advantages as bioprotectants and food additives. Trehalose-based imaging probes and inhibitors are already useful as research tools and may have future value in the diagnosis and treatment of tuberculosis, among other uses. Underlying the advancements made in these areas are novel synthetic methods that facilitate access to and evaluation of trehalose analogues. In this review, we focus on both aspects of the development of this class of molecules. First, we consider the chemical and chemoenzymatic methods that have been used to prepare trehalose analogues and discuss their prospects for synthesis on commercially relevant scales. Second, we describe ongoing efforts to develop and deploy detectable trehalose analogues, trehalose-based inhibitors, and non-digestible trehalose analogues. The current and potential future uses of these compounds are discussed, with an emphasis on their roles in understanding and combatting mycobacterial infection.

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“…With the inverting TP, for example, the synthesis of trehalose analogues such as ␣-galactosyl-1,1-␣-glucoside has been reported (8), a product that shows potential as prebiotic in food preparations as it shows inhibitory effects on intestinal disaccharidases (20). Interestingly, the glycosyl donor used in these reactions is much cheaper than the nucleotide sugars required by glycosyl transferases, which could be crucial for commercial success.…”

mentioning

confidence: 99%

Enzymatic Properties and Substrate Specificity of the Trehalose Phosphorylase from Caldanaerobacter subterraneus

Borght

Chen

Hoflack

et al. 2011

Appl Environ Microbiol

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A putative glycoside phosphorylase from Caldanaerobacter subterraneus subsp. pacificus was recombinantly expressed in Escherichia coli, after codon optimization and chemical synthesis of the encoding gene. The enzyme was purified by His tag chromatography and was found to be specifically active toward trehalose, with an optimal temperature of 80°C. In addition, no loss of activity could be detected after 1 h of incubation at 65°C, which means that it is the most stable trehalose phosphorylase reported so far. The substrate specificity was investigated in detail by measuring the relative activity on a range of alternative acceptors, applied in the reverse synthetic reaction, and determining the kinetic parameters for the best acceptors. These results were rationalized based on the enzyme-substrate interactions observed in a homology model with a docked ligand. The specificity for the orientation of the acceptor's hydroxyl groups was found to decrease in the following order: C-3 > C-2 > C-4. This results in a particularly high activity on the monosaccharides D-fucose, D-xylose, L-arabinose, and D-galactose, as well as on L-fucose. However, determination of the kinetic parameters revealed that these acceptors bind less tightly in the active site than the natural acceptor D-glucose, resulting in drastically increased K m values. Nevertheless, the enzyme's high thermostability and broad acceptor specificity make it a valuable candidate for industrial disaccharide synthesis.

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Enzymatic synthesis of a galactose-containing trehalose analogue disaccharide by Pyrococcus horikoshii trehalose-synthesizing glycosyltransferase: Inhibitory effects on several disaccharidase activities

Cited by 24 publications

References 21 publications

Structural Insights on the New Mechanism of Trehalose Synthesis by Trehalose Synthase TreT from Pyrococcus horikoshii

Structural Insights on the New Mechanism of Trehalose Synthesis by Trehalose Synthase TreT from Pyrococcus horikoshii

Tailoring trehalose for biomedical and biotechnological applications

Enzymatic Properties and Substrate Specificity of the Trehalose Phosphorylase from Caldanaerobacter subterraneus

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