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实验室定向进化立体选择性酶:不对称反应的多产催化剂来源。

Laboratory evolution of stereoselective enzymes: a prolific source of catalysts for asymmetric reactions.

机构信息

Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany.

出版信息

Angew Chem Int Ed Engl. 2011 Jan 3;50(1):138-74. doi: 10.1002/anie.201000826.

DOI:10.1002/anie.201000826
PMID:20715024
Abstract

Asymmetric catalysis plays a key role in modern synthetic organic chemistry, with synthetic catalysts and enzymes being the two available options. During the latter part of the last century the use of enzymes in organic chemistry and biotechnology experienced a period of rapid growth. However, these biocatalysts have traditionally suffered from several limitations, including in many cases limited substrate scope, poor enantioselectivity, insufficient stability, and sometimes product inhibition. During the last 15 years, the genetic technique of directed evolution has been developed to such an extent that all of these long-standing problems can be addressed and solved. It is based on repeated cycles of gene mutagenesis, expression, and screening (or selection). This Review focuses on the directed evolution of enantioselective enzymes, which constitutes a fundamentally new approach to asymmetric catalysis. Emphasis is placed on the development of methods to make laboratory evolution faster and more efficient, thus providing chemists and biotechnologists with a rich and non-ending source of robust and selective catalysts for a variety of useful applications.

摘要

不对称催化在现代合成有机化学中起着关键作用,其中合成催化剂和酶是两种可用的选择。在过去的一个世纪后半叶,酶在有机化学和生物技术中的应用经历了快速发展的时期。然而,这些生物催化剂传统上存在一些局限性,包括在许多情况下底物范围有限、对映选择性差、稳定性不足,有时还存在产物抑制。在过去的 15 年中,定向进化的遗传技术已经发展到这样的程度,所有这些长期存在的问题都可以得到解决。它基于基因诱变、表达和筛选(或选择)的反复循环。本文综述了对映选择性酶的定向进化,这是不对称催化的一种全新方法。重点介绍了使实验室进化更快、更有效的方法,从而为化学家提供了丰富且源源不断的用于各种有用应用的强大和选择性催化剂。

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