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利用生物大分子的最新蛋白质工程方法:从固定化到实施观点的综述。

State-of-the-art protein engineering approaches using biological macromolecules: A review from immobilization to implementation view point.

机构信息

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Tecnologico de Monterrey, School of Engineering and Sciences, Campus Monterrey, Ave. Eugenio Garza Sada 2501, Monterrey, N.L., CP 64849, Mexico.

出版信息

Int J Biol Macromol. 2018 Mar;108:893-901. doi: 10.1016/j.ijbiomac.2017.10.182. Epub 2017 Nov 2.

DOI:10.1016/j.ijbiomac.2017.10.182
PMID:29102791
Abstract

Over the past years, technological and scientific advances have proven biocatalysis as a sustainable alternative than traditional chemical catalysis including organo- or metallocatalysis. In this context, immobilization based approaches represent simple but effective routes for engineering enzyme catalysts with higher activities than wild-type derivatives. Many enzymes including oxidoreductases have been engineered by rational and directed evolution, to realize the catalytic activity, enantioselectivity, and stability attributes which are essential for their biotechnological exploitation. Induce yet stable activity in enzyme catalysis offer new insights and motivation to engineer efficient catalysts for practical and commercial purposes. It has now become possible to envisage substrate accessibility to the catalytic site of the enzyme by current computational capabilities that reduce the experimental work related to the enzyme selection, screening, and engineering. Herein, state-of-the-art protein engineering approaches for improving enzymatic activities including chemical modification, directed evolution, and rational design or their combination methods are discussed. The emphasis is also given to the applications of the resulting tailored catalysts ranging from fine chemicals to novel pharmaceutical compounds that use biocatalysts as a vital step.

摘要

在过去的几年中,技术和科学的进步已经证明,生物催化是一种比传统的有机或金属催化更可持续的替代方法。在这种情况下,基于固定化的方法是一种简单而有效的途径,可以用于工程化酶催化剂,使其具有比野生型衍生物更高的活性。许多酶,包括氧化还原酶,已经通过理性和定向进化进行了工程化,以实现其生物技术利用所必需的催化活性、对映选择性和稳定性特性。在酶催化中诱导稳定的活性为工程化高效催化剂提供了新的见解和动力,以实现实际和商业目的。现在,通过当前的计算能力,可以设想酶催化中底物对催化部位的可及性,从而减少与酶选择、筛选和工程相关的实验工作。本文讨论了用于提高酶活性的最新蛋白质工程方法,包括化学修饰、定向进化和合理设计或它们的组合方法。重点还放在经过修饰的催化剂的应用上,这些催化剂的应用范围从精细化学品到新型药物化合物,生物催化剂是其中至关重要的一步。

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