Sequestration-based bistability enables tuning of the switching boundaries and design of a latch.
Sequestration-based bistability enables tuning of the switching boundaries and design of a latch.
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DOI：
10.1038/msb.2012.52
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发表时间：
2012
影响因子：
9.9
通讯作者：
Arkin AP
中科院分区：
文献类型：
--
作者：
Chen D;Arkin AP
自然生物系统已经进化出多种开关来实现其环境响应和发展策略。合成生物学的新兴应用已经开始利用此类开关来实现日益复杂的设计行为。然而，并非所有开关架构都允许轻松设计开关和存储器属性。此外，并非所有设计都是由存在大量变体系列的组件构建的，这是构建许多正交开关变体的要求。因此，基因工程师迫切需要可扩展的策略来产生定制的双稳态开关。在这里，我们使用西格玛因子及其同源反西格玛因子来通过实验验证隔离产生的超灵敏性与正反馈相结合足以构建双稳态开关。我们证明，隔离使我们能够可预测地调整开关边界，并且我们可以轻松地将开关调整为设置复位锁存器，可以通过感应器输入脉冲在两种状态之间切换。
Natural biological systems have evolved a diverse array of switches to realize their strategies for environmental response and development. Emerging applications of synthetic biology have begun to exploit such switches to achieve increasingly sophisticated designed behaviors. However, not all switch architectures allow facile design of the switching and memory properties. Furthermore, not all designs are built from components for which large families of variants exist, a requirement for building many orthogonal switch variants. Therefore, there is a critical need from genetic engineers for scalable strategies that yield custom bistable switches. Here, we use a sigma factor and its cognate anti-sigma factor to experimentally verify that ultrasensitivity from sequestration combined with positive feedback is sufficient to build a bistable switch. We show that sequestration allows us to predictably tune the switching boundaries, and we can easily tune our switch to function as a set–reset latch that can be toggled between two states by a pulse of inducer input.
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DOI：
10.1073/pnas.0500345102
发表时间：
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影响因子：
11.1
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通讯作者：
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