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Biomolecular Systems Engineering: Unlocking the Potential of Engineered Allostery via the Lactose Repressor Topology
Annual Review of Biophysics ( IF 10.4 ) Pub Date : 2021-05-06 , DOI: 10.1146/annurev-biophys-090820-101708
Thomas M. Groseclose 1 , Ronald E. Rondon 1 , Ashley N. Hersey 1 , Prasaad T. Milner 1 , Dowan Kim 1 , Fumin Zhang 2 , Matthew J. Realff 1 , Corey J. Wilson 1
Affiliation  

Allosteric function is a critical component of many of the parts used to construct gene networks throughout synthetic biology. In this review, we discuss an emerging field of research and education, biomolecular systems engineering, that expands on the synthetic biology edifice—integrating workflows and strategies from protein engineering, chemical engineering, electrical engineering, and computer science principles. We focus on the role of engineered allosteric communication as it relates to transcriptional gene regulators—i.e., transcription factors and corresponding unit operations. In this review, we (a) explore allosteric communication in the lactose repressor LacI topology, (b) demonstrate how to leverage this understanding of allostery in the LacI system to engineer non-natural BUFFER and NOT logical operations, (c) illustrate how engineering workflows can be used to confer alternate allosteric functions in disparate systems that share the LacI topology, and (d) demonstrate how fundamental unit operations can be directed to form combinational logical operations.

中文翻译:


生物分子系统工程:通过乳糖阻遏物拓扑释放工程化的变构潜力

变构功能是整个合成生物学中用于构建基因网络的许多部分的关键组成部分。在这篇综述中,我们讨论了研究和教育的新兴领域,即生物分子系统工程,该领域扩展了合成生物学大厦-整合了蛋白质工程,化学工程,电气工程和计算机科学原理的工作流程和策略。我们关注工程化的变构通讯的作用,因为它与转录基因调节剂有关,即转录因子和相应的单位操作。在本综述中,我们(a)探索乳糖阻遏物LacI拓扑中的变构通讯,(b)演示如何利用对LacI系统中变构的理解来设计非自然BUFFER和NOT逻辑运算,(c)说明如何在共享LacI拓扑的不同系统中使用工程工作流来赋予替代变构功能,以及d)演示如何将基本单元操作定向为组合逻辑操作。

更新日期:2021-05-07
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