Strategies for designing biocatalysts with new functions

Strategies for designing biocatalysts with new functions
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设计具有新功能的生物催化剂的策略

DOI:
10.1039/d3cs00972f
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发表时间:
2024
影响因子:
46.2
通讯作者:
Bell E
Bell E
中科院分区:
化学1区
文献类型:
--
作者:
Bell E

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天然酶的工程化已经导致了广泛的生物催化剂的可用性,这些生物催化剂可用于各种化学品和药物的可持续制造。然而,对于许多重要的化学转化,没有已知的酶可以作为生物催化剂开发的起始模板。这些限制促使人们努力在蛋白质中构建全新的催化位点,以产生功能超出自然界的酶。这种自下而上的酶开发方法也可以揭示有效蛋白质催化的分子起源的新的基本见解。在本教程中,我们将调查已探索设计新的蛋白质催化剂的不同策略。这些方法将通过关键的例子来说明,这些例子展示了如何通过实验蛋白质工程和/或计算设计来开发高度熟练和选择性的生物催化剂。鉴于该领域的快速发展,我们乐观地认为,设计酶将开始发挥越来越突出的作用,作为工业生物催化剂在未来几年。
The engineering of natural enzymes has led to the availability of a broad range of biocatalysts that can be used for the sustainable manufacturing of a variety of chemicals and pharmaceuticals. However, for many important chemical transformations there are no known enzymes that can serve as starting templates for biocatalyst development. These limitations have fuelled efforts to build entirely new catalytic sites into proteins in order to generate enzymes with functions beyond those found in Nature. This bottom-up approach to enzyme development can also reveal new fundamental insights into the molecular origins of efficient protein catalysis. In this tutorial review, we will survey the different strategies that have been explored for designing new protein catalysts. These methods will be illustrated through key selected examples, which demonstrate how highly proficient and selective biocatalysts can be developed through experimental protein engineering and/or computational design. Given the rapid pace of development in the field, we are optimistic that designer enzymes will begin to play an increasingly prominent role as industrial biocatalysts in the coming years.
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