O'Loughlin Taryn L, Patrick Wayne M, Matsumura Ichiro
Department of Biochemistry, Center for Fundamental and Applied Molecular Evolution, Emory University, Atlanta, GA 30322, USA.
Protein Eng Des Sel. 2006 Oct;19(10):439-42. doi: 10.1093/protein/gzl029. Epub 2006 Jul 25.
Natural selection generally produces specific and efficient enzymes. In contrast, directed evolution experiments usually produce enzyme variants with broadened substrate specificity or enhanced catalytic promiscuity. Some proteins may be more evolvable than others, but few workers consider this problem when choosing starting points for laboratory evolution. Here, we review the variables associated with enzyme evolvability, namely promiscuity and mutational robustness. We present a qualitative model of adaptive evolution and recommend that protein engineers exploit their knowledge of natural history to identify evolvable wild-type proteins. Three examples of 'generalist' proteins that evolved in the laboratory into 'specialists' are described to illustrate the practical utility of this point.
自然选择通常会产生特异性强且高效的酶。相比之下，定向进化实验通常会产生具有拓宽底物特异性或增强催化多效性的酶变体。某些蛋白质可能比其他蛋白质更具进化潜力，但很少有研究人员在为实验室进化选择起始点时考虑这个问题。在这里，我们回顾了与酶进化潜力相关的变量，即多效性和突变稳健性。我们提出了一个适应性进化的定性模型，并建议蛋白质工程师利用他们对自然史的了解来识别具有进化潜力的野生型蛋白质。文中描述了三个在实验室中从“多面手”蛋白质进化为“专家型”蛋白质的例子，以说明这一点的实际应用价值。
