Cofactor‐Driven Cascade Reactions Enable the Efficient Preparation of Sugar Nucleotides

Wen, Liuqing; Yuan, Zheng; Zhang, Jiabinq; Meisner, Jeffrey; Li, Wanjin; Luo, Yawen; Wei, Fangyu

doi:10.1002/anie.202115696

Cited by 11 publications

(6 citation statements)

References 97 publications

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“…33−36 Recently, UDP-GlcNAc-derived sugar nucleotides have been succesfully prepared. 37 Here, we aim to synthesize UDP-D-Glc/GDP-D-Man-derived sugar nucleotides from common sugars. The chosen targets are listed in Figure S2, which cover the most reported sugar nucleotides that derive from both common sugar nucleotides.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…As mentioned above, de novo biosynthesis from existing common sugar nucleotides produces the majority of sugar nucleotides in nature. − UDP-D-GlcNAc, UDP-D-Glc, and GDP-D-Man are the three most common sugar nucleotides that often convert to other sugar nucleotides in living organisms. − Recently, UDP-GlcNAc-derived sugar nucleotides have been succesfully prepared . Here, we aim to synthesize UDP-D-Glc/GDP-D-Man-derived sugar nucleotides from common sugars.…”

Section: Methodsmentioning

confidence: 99%

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Facile Synthesis of Sugar Nucleotides from Common Sugars by the Cascade Conversion Strategy

et al. 2022

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Sugar nucleotides are essential glycosylation donors in the carbohydrate metabolism. Naturally, most sugar nucleotides are derived from a limited number of common sugar nucleotides by de novo biosynthetic pathways, undergoing single or multiple reactions such as dehydration, epimerization, isomerization, oxidation, reduction, amination, and acetylation reactions. However, it is widely believed that such complex bioconversions are not practical for synthetic use due to the high preparation cost and great difficulties in product isolation. Therefore, most of the discovered sugar nucleotides are not readily available. Here, based on de novo biosynthesis mainly, 13 difficult-to-access sugar nucleotides were successfully prepared from two common sugars D-Man and sucrose in high yields, at a multigram scale, and without the need for tedious purification manipulations. This work demonstrated that de novo biosynthesis, although undergoing complex reactions, is also practical and cost-effective for synthetic use by employing a cascade conversion strategy.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Facile Synthesis of Sugar Nucleotides from Common Sugars by the Cascade Conversion Strategy

et al. 2022

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“…UDP-GlcNAc was prepared from D-GlcNAc as reported previously ( Zheng et al, 2022 ). UDP-Glc and UDP-GlcA were prepared from Sucrose ( Wang et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Identification of a carbohydrate recognition motif of purinergic receptors

Zhao,

Wei,

et al. 2023

eLife

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As a major class of biomolecules, carbohydrates play indispensable roles in various biological processes. However, it remains largely unknown how carbohydrates directly modulate important drug targets, such as G-protein coupled receptors (GPCRs). Here, we employed P2Y purinoceptor 14 (P2Y14), a drug target for inflammation and immune responses, to uncover the sugar nucleotide activation of GPCRs. Integrating molecular dynamics simulation with functional study, we identified the uridine diphosphate (UDP)-sugar-binding site on P2Y14, and revealed that a UDP-glucose might activate the receptor by bridging the transmembrane (TM) helices 2 and 7. Between TM2 and TM7 of P2Y14, a conserved salt bridging chain (K2.60-D2.64-K7.35-E7.36 [KDKE]) was identified to distinguish different UDP-sugars, including UDP-glucose, UDP-galactose, UDP-glucuronic acid, and UDP-N-acetylglucosamine. We identified the KDKE chain as a conserved functional motif of sugar binding for both P2Y14 and P2Y purinoceptor 12 (P2Y12), and then designed three sugar nucleotides as agonists of P2Y12. These results not only expand our understanding for activation of purinergic receptors but also provide insights for the carbohydrate drug development for GPCRs.

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“…Recently, it was reported that such cost-effectiveness (and hence viability for multienzyme cascades) had been further improved through regeneration of the required cofactors (NADH, NADPH, NAD + , PMP, and acetyl-CoA, Figure ). , This has recently been exemplified through the synthesis of 25 challenging to access NDP-sugars starting from mannose, sucrose, and N -acetylglucosamine, in high yield, on a multigram scale, and without the need for purifications. , Additionally, the use of polyphosphate kinase (PPK3) or pyruvate kinase (PK) allows for the regeneration of the nucleotide triphosphates using phosphate glass or phosphoenolpyruvic acid (PEP) as sources of phosphate (Figure ). − Both methods were effective at regenerating ATP used by sugar kinases and UTP/GTP utilized by NDP-sugar pyrophosphorylases.…”

Section: Using Biocatalysis To Provide the Building Blocks For Bioche...mentioning

confidence: 99%

“…Recently, it was reported that such cost-effectiveness (and hence viability for multienzyme cascades) had been further improved through regeneration of the required cofactors (NADH, NADPH, NAD + , PMP, and acetyl-CoA, Figure 2 ). 81 , 82 This has recently been exemplified through the synthesis of 25 challenging to access NDP-sugars starting from mannose, sucrose, and N -acetylglucosamine, in high yield, on a multigram scale, and without the need for purifications. 81 , 82 Additionally, the use of polyphosphate kinase (PPK3) or pyruvate kinase (PK) allows for the regeneration of the nucleotide triphosphates using phosphate glass or phosphoenolpyruvic acid (PEP) as sources of phosphate ( Figure 2 ).…”

Section: Using Biocatalysis To Provide the Building Blocks For Bioche...mentioning

confidence: 99%

Biocatalytic Approaches to Building Blocks for Enzymatic and Chemical Glycan Synthesis

Dolan

Cosgrove

Miller

2022

JACS Au

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While the field of biocatalysis has bloomed over the past 20−30 years, advances in the understanding and improvement of carbohydrate-active enzymes, in particular, the sugar nucleotides involved in glycan building block biosynthesis, have progressed relatively more slowly. This perspective highlights the need for further insight into substrate promiscuity and the use of biocatalysis fundamentals (rational design, directed evolution, immobilization) to expand substrate scopes toward such carbohydrate building block syntheses and/or to improve enzyme stability, kinetics, or turnover. Further, it explores the growing premise of using biocatalysis to provide simple, cost-effective access to stereochemically defined carbohydrate materials, which can undergo late-stage chemical functionalization or automated glycan synthesis/polymerization.

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Cofactor‐Driven Cascade Reactions Enable the Efficient Preparation of Sugar Nucleotides

Cited by 11 publications

References 97 publications

Facile Synthesis of Sugar Nucleotides from Common Sugars by the Cascade Conversion Strategy

Facile Synthesis of Sugar Nucleotides from Common Sugars by the Cascade Conversion Strategy

Identification of a carbohydrate recognition motif of purinergic receptors

Biocatalytic Approaches to Building Blocks for Enzymatic and Chemical Glycan Synthesis

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