Biosensor libraries harness large classes of binding domains for construction of allosteric transcriptional regulators.
Biosensor libraries harness large classes of binding domains for construction of allosteric transcriptional regulators.
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DOI：
10.1038/s41467-018-05525-6
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发表时间：
2018-08-06
影响因子：
16.6
通讯作者：
Church GM
中科院分区：
文献类型：
--
作者：
Juárez JF;Lecube-Azpeitia B;Brown SL;Johnston CD;Church GM
细菌在其环境中感知特定分子并据此触发代谢反应的能力是一种宝贵的生物技术资源。虽然已经研究了许多介导这些过程的转录因子（TF），但只有少数被用于分子生物学应用。为了扩大生物技术相关传感器的库，我们提出了一种策略，用于构建和测试嵌合TF库，基于高度可溶性周质结合蛋白（PBP）与DNA结合域（DBD）的融合。我们通过构建和功能测试两种独特的苯甲酸盐（一种环境和工业相关代谢物）的感测和响应调节剂来验证这一概念。这项工作将使定制的生物传感器的新的合成调节电路的发展。细菌编码的环境传感器蛋白是潜在的转录控制的丰富来源，但只有少数已被利用的生物技术应用。在这里，作者开发了一个通用的策略，设计定制的单基因合成传感器和验证的方法，通过设计两个感测和响应调节苯甲酸。
The ability of bacteria to sense specific molecules within their environment and trigger metabolic responses in accordance is an invaluable biotechnological resource. While many transcription factors (TFs) mediating such processes have been studied, only a handful have been leveraged for molecular biology applications. To expand the repertoire of biotechnologically relevant sensors we present a strategy for the construction and testing of chimeric TF libraries, based on the fusion of highly soluble periplasmic binding proteins (PBPs) with DNA-binding domains (DBDs). We validate this concept by constructing and functionally testing two unique sense-and-respond regulators for benzoate, an environmentally and industrially relevant metabolite. This work will enable the development of tailored biosensors for novel synthetic regulatory circuits. Bacterially encoded environmental sensor proteins are potentially a rich source of transcriptional control but only a few have been harnessed for biotechnological applications. Here the authors develop a general strategy for designing custom-made monogenic synthetic sensors and validate the approach by designing two sense-and-respond regulators for benzoate.
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影响因子：
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