Biosynthesis of novel anticoagulant substances, α-salicin and α-isosalicin, using sucrose phosphorylase

IF 2.4 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Carbohydrate Research Pub Date : 2025-05-21 DOI:10.1016/j.carres.2025.109547

Yuxin Cheng , Jingjing Sun , Wei Wang , Chengcheng Jiang , Jianhua Hao

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引用次数: 0

Abstract

This study reports the enzymatic synthesis of novel anticoagulant glycosides, α-salicin and α-isosalicin, through the transglycosylation of o-hydroxybenzyl alcohol (salicyl alcohol) catalyzed by marine-derived sucrose phosphorylase Suc75290. Under optimized conditions (240 g/L sucrose, 12 g/L o-hydroxybenzyl alcohol, 150 U/mL enzyme, pH 7.5, 45 °C, 20 h), a conversion rate of 79.17 ± 0.64 % was achieved, yielding 8.57 ± 0.33 g/L α-salicin and 0.52 ± 0.19 g/L α-isosalicin. Structural characterization by NMR confirmed the α-configuration of both compounds. In vitro anticoagulant assays demonstrated that these glycosides significantly prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT), while reducing fibrinogen (FIB) levels, indicating dual inhibition of intrinsic and extrinsic coagulation pathways. Molecular docking revealed key interactions between salicyl alcohol and Suc75290's active site. This work establishes an efficient enzymatic route to α-anomeric salicin analogs with therapeutic potential, circumventing the limitations of chemical synthesis. These two novel anticoagulant glycoside compounds enzymatically synthesized provide new research ideas for the development of anticoagulant drugs.

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利用蔗糖磷酸化酶生物合成新型抗凝血物质α-水杨苷和α-异水杨苷

本研究报道了由海洋蔗糖磷酸化酶su75290催化邻羟基苄基醇（水杨醇）转糖基化，酶促合成新型抗凝血苷α-水杨苷和α-异水杨苷。优化条件为：蔗糖240 g/L、邻羟基苄醇12 g/L、酶150 U/mL、pH 7.5、45℃、20 h，转化率为79.17±0.64%，产率为8.57±0.33 g/L α-水杨苷和0.52±0.19 g/L α-异水杨苷。核磁共振结构表征证实了两种化合物的α-构型。体外抗凝试验表明，这些糖苷显著延长了活化的部分凝血活酶时间（APTT）、凝血酶原时间（PT）和凝血酶时间（TT），同时降低了纤维蛋白原（FIB）水平，表明了内在和外在凝血途径的双重抑制。分子对接揭示了水杨醇与su75290活性位点之间的关键相互作用。这项工作建立了一个有效的酶促α-氨基水杨苷类似物的治疗潜力，绕过了化学合成的限制。这两种新型抗凝血苷类化合物的酶法合成为抗凝血药物的开发提供了新的研究思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Carbohydrate Research 化学-生化与分子生物学

CiteScore

5.00

自引率

3.20%

发文量

183

审稿时长

3.6 weeks

期刊介绍： Carbohydrate Research publishes reports of original research in the following areas of carbohydrate science: action of enzymes, analytical chemistry, biochemistry (biosynthesis, degradation, structural and functional biochemistry, conformation, molecular recognition, enzyme mechanisms, carbohydrate-processing enzymes, including glycosidases and glycosyltransferases), chemical synthesis, isolation of natural products, physicochemical studies, reactions and their mechanisms, the study of structures and stereochemistry, and technological aspects. Papers on polysaccharides should have a "molecular" component; that is a paper on new or modified polysaccharides should include structural information and characterization in addition to the usual studies of rheological properties and the like. A paper on a new, naturally occurring polysaccharide should include structural information, defining monosaccharide components and linkage sequence. Papers devoted wholly or partly to X-ray crystallographic studies, or to computational aspects (molecular mechanics or molecular orbital calculations, simulations via molecular dynamics), will be considered if they meet certain criteria. For computational papers the requirements are that the methods used be specified in sufficient detail to permit replication of the results, and that the conclusions be shown to have relevance to experimental observations - the authors'' own data or data from the literature. Specific directions for the presentation of X-ray data are given below under Results and "discussion".