Mannervik Bengt, Runarsdottir Arna, Kurtovic Sanela
Department of Biochemistry and Organic Chemistry, Uppsala University, BMC 576, SE-75123 Uppsala, Sweden.
Biochem Soc Trans. 2009 Aug;37(Pt 4):740-4. doi: 10.1042/BST0370740.
A functional enzyme displays activity with at least one substrate and can be represented by a vector in substrate-activity space. Many enzymes, including GSTs (glutathione transferases), are promiscuous in the sense that they act on alternative substrates, and the corresponding vectors operate in multidimensional space. The direction of the vector is governed by the relative activities of the diverse substrates. Stochastic mutations of already existing enzymes generate populations of variants, and clusters of functionally similar mutants can serve as parents for subsequent generations of enzymes. The proper evolving unit is a functional quasi-species, which may not be identical with the 'best' variant in its generation. The manifestation of the quasi-species is dependent on the substrate matrix used to explore catalytic activities. Multivariate analysis is an approach to identifying quasi-species and to investigate evolutionary trajectories in the directed evolution of enzymes for novel functions.
一种功能性酶对至少一种底物具有活性，并且可以由底物 - 活性空间中的一个向量表示。许多酶，包括谷胱甘肽转移酶（GSTs），具有多底物特异性，即它们作用于多种替代底物，相应的向量在多维空间中起作用。向量的方向由不同底物的相对活性决定。现有酶的随机突变产生变异体群体，功能相似的突变体簇可作为后续几代酶的亲本。合适的进化单元是一个功能性准种，它可能与其所在世代中的“最佳”变异体不同。准种的表现取决于用于探索催化活性的底物矩阵。多变量分析是一种识别准种并研究用于新功能的酶定向进化中进化轨迹的方法。
