Facile Enzymatic Synthesis of Ketoses

Wen, Liuqing; Huang, Kenneth; Wei, Mohui; Meisner, Jeffrey; Liu, Yunpeng; Garner, Kristina; Zang, Lanlan; Wang, Xuan; Li, Xu; Fang, Junqiang; Zhang, Houcheng; Wang, Peng George

doi:10.1002/anie.201505714

Cited by 66 publications

(54 citation statements)

References 39 publications

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“…Rare sugars can be used as starting materials for the synthesis of potential natural products with important biological activities for applications in the food, pharmaceutical, medicinal, and chemical industries 1, 2 . Sugar 4-epimerization is a valuable reaction for the production of rare sugars and their derivatives.…”

Section: Introductionmentioning

confidence: 99%

Structure-based prediction and identification of 4-epimerization activity of phosphate sugars in class II aldolases

Lee

Hong

et al. 2017

Sci Rep

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Sugar 4-epimerization reactions are important for the production of rare sugars and their derivatives, which have various potential industrial applications. For example, the production of tagatose, a functional sweetener, from fructose by sugar 4-epimerization is currently constrained because a fructose 4-epimerase does not exist in nature. We found that class II d-fructose-1,6-bisphosphate aldolase (FbaA) catalyzed the 4-epimerization of d-fructose-6-phosphate (F6P) to d-tagatose-6-phosphate (T6P) based on the prediction via structural comparisons with epimerase and molecular docking and the identification of the condensed products of C3 sugars. In vivo, the 4-epimerization activity of FbaA is normally repressed. This can be explained by our results showing the catalytic efficiency of d-fructose-6-phosphate kinase for F6P phosphorylation was significantly higher than that of FbaA for F6P epimerization. Here, we identified the epimerization reactions and the responsible catalytic residues through observation of the reactions of FbaA and l-rhamnulose-1-phosphate aldolases (RhaD) variants with substituted catalytic residues using different substrates. Moreover, we obtained detailed potential epimerization reaction mechanism of FbaA and a general epimerization mechanism of the class II aldolases l-fuculose-1-phosphate aldolase, RhaD, and FbaA. Thus, class II aldolases can be used as 4-epimerases for the stereo-selective synthesis of valuable carbohydrates.

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Section: Introductionmentioning

confidence: 99%

Structure-based prediction and identification of 4-epimerization activity of phosphate sugars in class II aldolases

Lee

Hong

et al. 2017

Sci Rep

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“…18 We recently found that DTE from Pseudomonas Sp, St-24 also fails to use many ketose phosphates as the substrate. 19–20 Therefore, we proposed that it may not recognize 6-deoxy-L-psicose 1-phosphate as substrate in this work. This assumption is supported by the purity analysis of 6-deoxy-L-psicose (Table 1).…”

mentioning

confidence: 95%

“…19 The main advantage of this method is that the products could be obtained in both high yield and purity without having to undergo an isomer separation step. The principle of this strategy is based on a “phosphorylation→dephosphorylation” cascade reaction.…”

mentioning

confidence: 99%

Two-step enzymatic synthesis of 6-deoxy-l-psicose

Wen

Huang

Zheng

et al. 2016

Tetrahedron Letters

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Rare sugars offer a plethora of applications in the pharmaceutical, medicinal, and industries, as well as in synthetic chemistry. However, studies of rare sugars have been hampered by their relative scarcity. In this work, we describe a two-step strategy to efficiently and conveniently prepare 6-deoxy-L-psicose from L-rhamnose. In the first reaction step, the isomerization of L-rhamnose (6-deoxy-L-mannose) to L-rhamnulose (6-deoxy-L-fructose) catalyzed by L-rhamnose isomerase (RhaI), and the epimerization of L-rhamnulose to 6-deoxy-L-psicose catalyzed by D-tagatose 3-epimerase (DTE) were coupled with selective phosphorylation reaction by fructose kinase from human (HK), which selectively phosphorylate 6-deoxy-L-psicose at C-1 position. 6-deoxy-L-psicose 1-phosphate was purified by a silver nitrate precipitation method. In the second step, the phosphate group of the 6-deoxy-L-sorbose 1-phosphate was hydrolyzed with acid phosphatase (AphA) to produce 6-deoxy-L-psicose in 81% yield with respect to L-rhamnose. This method allows that the 6-deoxy-L-psicose to be obtained from readily available starting materials with high purity and without having to undergo isomer separation.

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“…To address these problems, we recently developed a convenient, efficient and cost- effective platform for ketose synthesis, by which 10 non-readily available ketopentoses (L-ribulose, D-xylulose, D-ribulose, and L-xylulose) and ketohexoses (D-tagatose, D-sorbose, D-psicose, L-tagatose, L-fructose and L-psicose) were prepared from common and inexpensive starting materials with both high yield and purity without having to undergo a tedious isomer separation step. 15 The basic concept of this strategy is based on a “phosphorylation→dephosphorylation” cascade reaction. Thermodynamically unfavorable conversions were combined with targeted phosphorylation reactions by substrate-specific kinases to drive the conversions towards the formation of the desired ketoses.…”

mentioning

confidence: 99%

“…By screening the substrate specificity of many kinases, we recently found that fructose kinase (HK) from human, which phosphorylate ketose to ketose 1-phosphate, 26 preferred ketose with (3S)-configuration as its substrate. 15 In this work, substrate specificity of HK towards 6-deoxy-L-sorbose ((3S)-configuration), L-fucose ((3 R )-configuration), and L-fuculose ((3 R )-configuration) was studied (see Supplementary Information). 6-deoxy-L-sorbose could serve as the substrate of HK while no detectable activity of HK towards either L-fucose or L-fuculose was observed (Table 1), indicating its potential for one-pot multienzyme (OPME) reaction to produce 6-deoxy-L-sorbose from L-fucose.…”

mentioning

confidence: 99%

A two-step strategy for the preparation of 6-deoxy-l-sorbose

Wen

Huang

Zheng

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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A two-step enzymatic strategy for the efficient and convenient synthesis of 6-deoxy-L-sorbose was reported herein. In the first reaction step, the isomerization of L-fucose (6-deoxy-Lgalactose) to L-fuculose (6-deoxy-L-tagatose) catalyzed by L-fucose isomerase (FucI), and the epimerization of L-fuculose to 6-deoxy-L-sorbose catalyzed by D-tagatose 3-epimerase (DTE) were coupled with the targeted phosphorylation of 6-deoxy-L-sorbose by fructose kinase from human (HK) in a one-pot reaction. The resultant 6-deoxy-L-sorbose 1-phosphate was purified by silver nitrate precipitation method. In the second reaction step, the phosphate group of the 6-deoxy-L-sorbose 1-phosphate was hydrolyzed with acid phosphatase (AphA) to produce 6-deoxy-L-sorbose in 81% yield with regard to L-fucose.

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Facile Enzymatic Synthesis of Ketoses

Cited by 66 publications

References 39 publications

Structure-based prediction and identification of 4-epimerization activity of phosphate sugars in class II aldolases

Structure-based prediction and identification of 4-epimerization activity of phosphate sugars in class II aldolases

Two-step enzymatic synthesis of 6-deoxy-l-psicose

A two-step strategy for the preparation of 6-deoxy-l-sorbose

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