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在配体-活性空间中寻找分子准种及其在定向酶进化中的应用。

The quest for molecular quasi-species in ligand-activity space and its application to directed enzyme evolution.

机构信息

Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden.

出版信息

FEBS Lett. 2010 Jun 18;584(12):2565-71. doi: 10.1016/j.febslet.2010.04.024. Epub 2010 Apr 18.

DOI:10.1016/j.febslet.2010.04.024
PMID:20399208
Abstract

We propose that the proper evolving unit in enzyme evolution is not a single "fittest molecule", but a cluster of related variants denoted a "quasi-species". A distribution of variants provides genetic variability and thereby reduces the risk of inbreeding and evolutionary dead-ends. Different matrices of substrates or activity modulators will lead to different selection criteria and divergent evolutionary trajectories. We provide examples from our directed evolution of glutathione transferases illustrating the interplay between libraries of enzyme variants and ligand matrices in the identification of quasi-species. The ligand matrix is shown to be crucial to the outcome of the search for novel activities. In this sense the experimental system resembles the biological environment in governing the evolution of enzymes.

摘要

我们提出,在酶进化中,合适的进化单位不是单个的“最适分子”,而是一个相关变体簇,称为“准种”。变体的分布提供了遗传变异性,从而降低了近亲繁殖和进化死胡同的风险。不同的底物或活性调节剂矩阵将导致不同的选择标准和不同的进化轨迹。我们从我们的谷胱甘肽转移酶定向进化中提供了一些例子,说明了酶变体库和配体矩阵之间的相互作用在准种鉴定中的作用。配体矩阵对于发现新活性的搜索结果至关重要。从这个意义上说,实验系统类似于生物环境,它控制着酶的进化。

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