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体内基于蛋白质的生物传感器:实时观察新陈代谢

In vivo protein-based biosensors: seeing metabolism in real time.

作者信息

Alexandrov Kirill, Vickers Claudia E

机构信息

CSIRO-QUT Synthetic Biology Alliance, ARC Centre of Excellence in Synthetic Biology, Centre for Agriculture and the Bioeconomy, Centre for Genomics and Personalised Health, School of Biology and Environmental Science, Queensland University of Technology, Brisbane, QLD, 4001, Australia; CSIRO Future Science Platform in Synthetic Biology, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Dutton Park, Brisbane, QLD 4012, Australia.

CSIRO-QUT Synthetic Biology Alliance, ARC Centre of Excellence in Synthetic Biology, Centre for Agriculture and the Bioeconomy, Centre for Genomics and Personalised Health, School of Biology and Environmental Science, Queensland University of Technology, Brisbane, QLD, 4001, Australia; CSIRO Future Science Platform in Synthetic Biology, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Dutton Park, Brisbane, QLD 4012, Australia; Eden Brew, Brisbane, QLD 4001, Australia; Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.

出版信息

Trends Biotechnol. 2023 Jan;41(1):19-26. doi: 10.1016/j.tibtech.2022.07.002. Epub 2022 Jul 31.

DOI:10.1016/j.tibtech.2022.07.002
PMID:35918219
Abstract

Biological homeostasis is a dynamic and elastic equilibrium of countless interlinked biochemical reactions. A key goal of life sciences is to understand these dynamics; bioengineers seek to reconfigure such networks. Both goals require the ability to monitor the concentration of individual intracellular metabolites with sufficient spatiotemporal resolution. To achieve this, a range of protein or protein/DNA signalling circuits with optical readouts have been constructed. Protein biosensors can provide quantitative information at subsecond temporal and suborganelle spatial resolution. However, their construction is fraught with difficulties related to integrating the affinity- and selectivity-endowing components with the signal reporters. We argue that development of efficient approaches for construction of chemically induced dimerisation systems and reporter domains with large dynamic ranges will solve these problems.

摘要

生物稳态是无数相互关联的生化反应的动态弹性平衡。生命科学的一个关键目标是理解这些动态过程;生物工程师则试图重新配置此类网络。这两个目标都需要具备以足够的时空分辨率监测单个细胞内代谢物浓度的能力。为实现这一目标,人们构建了一系列具有光学读数的蛋白质或蛋白质/DNA信号传导回路。蛋白质生物传感器可以在亚秒级的时间分辨率和亚细胞器空间分辨率下提供定量信息。然而,其构建过程充满困难,这些困难与将赋予亲和力和选择性的组件与信号报告分子整合有关。我们认为,开发高效的化学诱导二聚化系统和具有大动态范围的报告结构域的构建方法将解决这些问题。

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