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用于合成核苷酸糖的酶级联反应:近期生产策略的更新

Enzyme cascades for the synthesis of nucleotide sugars: Updates to recent production strategies.

作者信息

Frohnmeyer Hannes, Elling Lothar

机构信息

Laboratory for Biomaterials, Institute of Biotechnology and Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstraße 20, 52074, Aachen, Germany.

Laboratory for Biomaterials, Institute of Biotechnology and Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstraße 20, 52074, Aachen, Germany.

出版信息

Carbohydr Res. 2023 Jan;523:108727. doi: 10.1016/j.carres.2022.108727. Epub 2022 Nov 29.

DOI:10.1016/j.carres.2022.108727
PMID:36521208
Abstract

Nucleotide sugars play an elementary role in nature as building blocks of glycans, polysaccharides, and glycoconjugates used in the pharmaceutical, cosmetics, and food industries. As substrates of Leloir-glycosyltransferases, nucleotide sugars are essential for chemoenzymatic in vitro syntheses. However, high costs and the limited availability of nucleotide sugars prevent applications of biocatalytic cascades on a large industrial scale. Therefore, the focus is increasingly on nucleotide sugar synthesis strategies to make significant application processes feasible. The chemical synthesis of nucleotide sugars and their derivatives is well established, but the yields of these processes are usually low. Enzyme catalysis offers a suitable alternative here, and in the last 30 years, many synthesis routes for nucleotide sugars have been discovered and used for production. However, many of the published procedures shy away from assessing the practicability of their processes. With this review, we give an insight into the development of the (chemo)enzymatic nucleotide sugar synthesis pathways of the last years and present an assessment of critical process parameters such as total turnover number (TTN), space-time yield (STY), and enzyme loading.

摘要

核苷酸糖在自然界中作为聚糖、多糖和糖缀合物的构建单元发挥着基本作用,这些物质被应用于制药、化妆品和食品工业。作为勒洛伊尔糖基转移酶的底物,核苷酸糖对于化学酶法体外合成至关重要。然而,核苷酸糖的高成本和有限的可得性阻碍了生物催化级联反应在大规模工业生产中的应用。因此,人们越来越关注核苷酸糖的合成策略,以使重要的应用过程可行。核苷酸糖及其衍生物的化学合成方法已经成熟,但这些方法的产率通常较低。酶催化在这里提供了一种合适的替代方法,在过去30年里,已经发现了许多核苷酸糖的合成路线并用于生产。然而,许多已发表的方法都回避了对其工艺实用性的评估。通过这篇综述,我们深入了解了近年来(化学)酶促核苷酸糖合成途径的发展,并对关键工艺参数进行了评估,如总周转数(TTN)、时空产率(STY)和酶负载量。

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