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核酸衍生物的多酶合成:总体概述。

Multienzymatic synthesis of nucleic acid derivatives: a general perspective.

作者信息

Fernández-Lucas Jesús

机构信息

Applied Biotechnology Group, Department of Pharmacy and Biotechnology, Faculty of Biomedical Sciences, European University of Madrid, Urbanización El Bosque, Calle Tajo, s/n, 28670, Villaviciosa de Odón, Madrid, Spain,

出版信息

Appl Microbiol Biotechnol. 2015 Jun;99(11):4615-27. doi: 10.1007/s00253-015-6642-x. Epub 2015 May 9.

DOI:10.1007/s00253-015-6642-x
PMID:25952113
Abstract

Living cells are most perfect synthetic factory. The surprising synthetic efficiency of biological systems is allowed by the combination of multiple processes catalyzed by enzymes working sequentially. In this sense, biocatalysis tries to reproduce nature's synthetic strategies to perform the synthesis of different organic compounds using natural catalysts such as cells or enzymes. Nowadays, the use of multienzymatic systems in biocatalysis is becoming a habitual strategy for the synthesis of organic compounds that leads to the realization of complex synthetic schemes. By combining several steps in one pot, a significant step economy can be realized and the potential for environmentally benign synthesis is improved. Using this sustainable synthetic system, several work-up steps can be avoided and pure products are ideally isolated after a series of reactions in one single vessel after just one straightforward purification step. In recent years, enzymatic methodology for the preparation of nucleic acid derivatives (NADs) has become a standard technique for the synthesis of a wide variety of natural NADs. Enzymatic methods have been shown to be an efficient alternative for the synthesis of nucleoside and nucleotide analogs to the traditional multistep chemical methods, since chemical glycosylation reactions include several protection-deprotection steps and the use of chemical reagents and organic solvents that are expensive and environmentally harmful. In this minireview, we want to illustrate what we consider the most current relevant examples of in vivo and in vitro multienzymatic systems used for the synthesis of nucleic acid derivatives showing advantages and disadvantages of each methodology. Finally, a detailed perspective about the impact of -omics in multienzymatic systems has been described.

摘要

活细胞是最完美的合成工厂。生物系统惊人的合成效率源于多种由酶依次催化的过程的结合。从这个意义上讲,生物催化试图重现自然界的合成策略,利用细胞或酶等天然催化剂来合成不同的有机化合物。如今,在生物催化中使用多酶系统正成为合成有机化合物的一种常用策略,这使得复杂的合成方案得以实现。通过在一个反应容器中合并多个步骤,可以实现显著的步骤经济性,并提高环境友好型合成的潜力。使用这种可持续的合成系统,可以避免几个后处理步骤,并且在一个单一容器中经过一系列反应后,只需一个简单的纯化步骤就能理想地分离出纯产品。近年来,用于制备核酸衍生物(NADs)的酶促方法已成为合成多种天然NADs的标准技术。酶促方法已被证明是合成核苷和核苷酸类似物的一种有效替代传统多步化学方法的方法,因为化学糖基化反应包括几个保护-脱保护步骤以及使用昂贵且对环境有害的化学试剂和有机溶剂。在本综述中,我们想举例说明我们认为用于合成核酸衍生物的体内和体外多酶系统的最新相关实例,展示每种方法的优缺点。最后,还描述了关于组学对多酶系统影响的详细观点。

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