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设计具有多个活性中心的人工酶:新趋势、新机遇和新问题。

Design of Artificial Enzymes Bearing Several Active Centers: New Trends, Opportunities and Problems.

机构信息

Departamento de Biocatálisis, ICP-CSIC, Campus UAM-CSIC, 28049 Madrid, Spain.

Student of Departamento de Biología Molecular, Universidad Autónoma de Madrid, C/Darwin 2, Campus UAM-CSIC, Cantoblanco, 28049 Madrid, Spain.

出版信息

Int J Mol Sci. 2022 May 10;23(10):5304. doi: 10.3390/ijms23105304.

DOI:10.3390/ijms23105304
PMID:35628115
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9141793/
Abstract

Harnessing enzymes which possess several catalytic activities is a topic where intense research has been carried out, mainly coupled with the development of cascade reactions. This review tries to cover the different possibilities to reach this goal: enzymes with promiscuous activities, fusion enzymes, enzymes + metal catalysts (including metal nanoparticles or site-directed attached organometallic catalyst), enzymes bearing non-canonical amino acids + metal catalysts, design of enzymes bearing a second biological but artificial active center (plurizymes) by coupling enzyme modelling and directed mutagenesis and plurizymes that have been site directed modified in both or in just one active center with an irreversible inhibitor attached to an organometallic catalyst. Some examples of cascade reactions catalyzed by the enzymes bearing several catalytic activities are also described. Finally, some foreseen problems of the use of these multi-activity enzymes are described (mainly related to the balance of the catalytic activities, necessary in many instances, or the different operational stabilities of the different catalytic activities). The design of new multi-activity enzymes (e.g., plurizymes or modified plurizymes) seems to be a topic with unarguable interest, as this may link biological and non-biological activities to establish new combo-catalysis routes.

摘要

利用具有多种催化活性的酶是一个研究热点,主要与级联反应的发展相结合。这篇综述试图涵盖实现这一目标的不同可能性:具有混杂活性的酶、融合酶、酶+金属催化剂(包括金属纳米粒子或定点附着的有机金属催化剂)、带有非典型氨基酸+金属催化剂的酶、通过酶建模和定向突变设计带有第二个生物但人工活性中心的酶(多酶),以及在两个或仅一个活性中心中用与有机金属催化剂相连的不可逆抑制剂定点修饰的多酶。还描述了一些由具有多种催化活性的酶催化的级联反应的例子。最后,还描述了使用这些多活性酶可能出现的一些问题(主要与许多情况下所需的催化活性的平衡有关,或不同催化活性的不同操作稳定性有关)。设计新的多活性酶(例如,多酶或修饰的多酶)似乎是一个具有无可争议的兴趣的课题,因为它可以将生物和非生物活性联系起来,建立新的组合催化途径。

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