计算机模拟进化的乳糖操纵子对人工诱导剂表现出双稳态，但对乳糖则不然。
In silico evolved lac operons exhibit bistability for artificial inducers, but not for lactose.
作者信息
van Hoek M J A, Hogeweg P
机构信息
Theoretical Biology/Bioinformatics Group, Utrecht University, Utrecht, The Netherlands.
出版信息
Biophys J. 2006 Oct 15;91(8):2833-43. doi: 10.1529/biophysj.105.077420. Epub 2006 Jul 28.
Bistability in the lac operon of Escherichia coli has been widely studied, both experimentally and theoretically. Experimentally, bistability has been observed when E. coli is induced by an artificial, nonmetabolizable, inducer. However, if the lac operon is induced with lactose, the natural inducer, bistability has not been demonstrated. We derive an analytical expression that can predict the occurrence of bistability both for artificial inducers and lactose. We find very different conditions for bistability in the two cases. Indeed, for artificial inducers bistability is predicted, but for lactose the condition for bistability is much more difficult to satisfy. Moreover, we demonstrate that in silico evolution of the lac operon generates an operon that avoids bistability with respect to lactose, but does exhibit bistability with respect to artificial inducers. The activity of this evolved operon strikingly resembles the experimentally observed activity of the operon. Thus our computational experiments suggest that the wild-type lac operon, which regulates lactose metabolism, is not a bistable switch. Nevertheless, for engineering purposes, this operon can be used as a bistable switch with artificial inducers.
大肠杆菌乳糖操纵子中的双稳态已在实验和理论上得到广泛研究。在实验中，当大肠杆菌由人工合成的、不可代谢的诱导剂诱导时，会观察到双稳态。然而，如果用天然诱导剂乳糖诱导乳糖操纵子，则尚未证明双稳态的存在。我们推导了一个解析表达式，它可以预测人工诱导剂和乳糖情况下双稳态的出现。我们发现这两种情况下双稳态的条件非常不同。事实上，对于人工诱导剂预测会出现双稳态，但对于乳糖，双稳态的条件要难得多才能满足。此外，我们证明乳糖操纵子的计算机模拟进化产生了一个操纵子，它避免了对乳糖的双稳态，但对人工诱导剂确实表现出双稳态。这个进化后的操纵子的活性与实验观察到的操纵子活性惊人地相似。因此，我们的计算实验表明，调节乳糖代谢的野生型乳糖操纵子不是一个双稳态开关。然而，出于工程目的，这个操纵子可以用作人工诱导剂的双稳态开关。
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