Lewkowicz Elizabeth S, Iribarren Adolfo M
Laboratorio de Biocatálisis y Biotransformaciones, Universidad Nacional de Quilmes, Bernal, Buenos Aires. Argentina.
Curr Pharm Des. 2017 Oct 11. doi: 10.2174/1381612823666171011101133.
Nucleosides constitute an extensive group of natural and chemically modified compounds that display a wide range of structures and activities. Different biocatalysts have been developed for their preparation, but the choice of commercially available enzymes is limited. Therefore, the search of new biocatalysts is particularly attractive. In this sense, microorganisms are a vast source of enzymatic diversity that can be directly used as a whole cell biocatalysts providing a potential cheaper and suitable route for industrial applications.
This work makes particular emphasis on the following methods: the biocatalyzed whole cell synthesis of nucleosides mediated by phosphorylases, key biocatalyzed steps involved in other chemoenzymatic routes to prepare nucleoside analogues and the transformation of nucleosides in derivatives with particular properties.
The literature covered in this work confirms that biocatalytic procedures that make use of whole cell systems can be successfully applied to obtain a wide variety of nucleoside analogues and their derivatives, providing alternative and complementary routes to traditional chemistry. The direct use of microbial whole cells as biocatalysts affords competitive results since it avoids the cumbersome procedures involved in enzyme isolation and facilitates multienzymatic processes. These biocatalysts also maintain the enzymes in their natural environment, protecting their activities from reaction conditions.
Although the information presented herein shows that these methodologies have reached a high degree of development, it is expected that future contributions of protein engineering and nucleoside metabolism knowledge, among other disciplines, will expand the already wide range of applications in nucleoside chemistry of whole cell biocatalysis.
核苷构成了一大类天然和化学修饰的化合物,它们具有广泛的结构和活性。人们已经开发出不同的生物催化剂来制备核苷,但市售酶的选择有限。因此,寻找新的生物催化剂特别具有吸引力。从这个意义上说,微生物是酶多样性的巨大来源,可以直接用作全细胞生物催化剂,为工业应用提供潜在的更便宜且合适的途径。
本工作特别强调以下方法:磷酸化酶介导的核苷生物催化全细胞合成、制备核苷类似物的其他化学酶促途径中涉及的关键生物催化步骤以及核苷向具有特定性质的衍生物的转化。
本工作涵盖的文献证实,利用全细胞系统的生物催化程序可以成功应用于获得多种核苷类似物及其衍生物,为传统化学提供替代和补充途径。直接使用微生物全细胞作为生物催化剂可产生具有竞争力的结果,因为它避免了酶分离中繁琐的程序,并促进了多酶过程。这些生物催化剂还将酶保持在其自然环境中,保护它们的活性免受反应条件的影响。
尽管本文提供的信息表明这些方法已经高度发展,但预计蛋白质工程和核苷代谢知识等其他学科未来的贡献将扩大全细胞生物催化在核苷化学中已经广泛的应用范围。