“时-空耦合”活细胞合成量子点

doi:10.12211/2096-8280.2021-059

合成生物学 ›› 2022, Vol. 3 ›› Issue (2): 385-398.DOI: 10.12211/2096-8280.2021-059

“时-空耦合”活细胞合成量子点

贾剑红¹, 杨玲玲², 刘安安¹, 庞代文¹

^1.南开大学药物化学生物学国家重点实验室，化学学院分析科学研究中心，天津市生物传感及分子识别重点实验室，天津　300071
^2.武汉大学高等研究院，化学与分子科学学院，湖北　武汉　430072

收稿日期:2021-05-08 修回日期:2021-05-29 出版日期:2022-04-30 发布日期:2022-05-11
通讯作者: 庞代文
作者简介:贾剑红（1994—），女，博士研究生。研究方向为纳米材料生物合成。E-mail：1076215263@qq.com
杨玲玲（1992—），女，博士研究生。研究方向为纳米生物医学分析。E-mail：doublelengyang@163.com
庞代文（1961—），男，教授，博士生导师。研究方向为生物医学分析化学、纳米生物技术、纳米光电显示技术等。E-mail：dwpang@whu.edu.cn
基金资助:
国家自然科学基金(91859123);国家重点研发计划(2019YFA0210103);中央高校基本科研业务费专项(63201024);天津市自然科学基金(19JCQNJC02400)

Space-time-coupled live-cell synthesis of quantum dots

Jianhong JIA¹, Lingling YANG², An’an LIU¹, Daiwen PANG¹

^1.State Key Laboratory of Medicinal Chemical Biology，College of Chemistry，Research Center for Analytical Science，Tianjin Key Laboratory of Biosensing and Molecular Recognition，Nankai University，Tianjin 300071，China
^2.The Institute for Advanced Studies，College of Chemistry and Molecular Sciences，Wuhan University，Wuhan 430072，Hubei，China

Received:2021-05-08 Revised:2021-05-29 Online:2022-04-30 Published:2022-05-11
Contact: Daiwen PANG

摘要/Abstract

摘要：

细胞是生命活动的基本单位。随着材料学、化学和生物学等多学科交叉日益加深，借助活细胞内代谢途径合成无机纳米材料的研究受到广泛关注，同时也拓展了合成生物学的研究领域。然而，活细胞合成无机纳米材料主要以胞内生物大分子为模板，且依赖单一生化反应途径，产物的尺寸、形貌和性质均难以人为调控。自2009年，本课题组通过人为设计、巧妙耦合活细胞内的硒代谢途径和重金属离子解毒途径，发展出“时-空耦合”活细胞合成策略，在真菌、细菌和哺乳动物细胞内原位合成了不同组成、尺寸和性能的无机半导体荧光纳晶（量子点）。在从物质和能量代谢的角度研究活细胞合成机理的基础上，将活细胞合成体系简化，设计构建了无细胞的准生物体系，成功合成了多种纳米材料，同时也验证了“时-空耦合”策略的正确性。本文将总结评述“时-空耦合”活细胞合成量子点的策略、机理及其在生物标记、生物成像和病原微生物与重金属离子检测等方面的应用，并简要介绍准生物体系。同时，将阐明目前活细胞合成策略面临的挑战。随着合成生物学的发展，通过“时-空耦合”活细胞合成策略可以将无机功能材料“自然地”融入生物体系，赋予生物体系超常的能力，拓展合成生物学。

关键词: 量子点, 活细胞, 合成, 代谢, 调控

Abstract:

As fundamental units of structure and function in all living organisms, cells grow and proliferate through intracellular metabolism. The metabolism is characterized by catabolism, through which cells break down complex molecules to produce energy and reducing power, and anabolism, through which cells use energy and reducing power to construct complex molecules for biological functions. Due to the development of interdisciplinary research in materials science, chemistry and biology, many new ideas and concepts inspired by biological systems have been proposed to synthesize various inorganic nanomaterials. Some bacteria, such as magnetotactic bacteria, have evolved to be able to synthesize inorganic nanomaterials. On the other hand, some inorganic-based skeletal structures can be synthesized by harnessing specific biomolecules as templates and the metabolic functions of live cells, which is well known as biomineralization. However, metabolic pathways in live cells are extremely complicated, and it is difficult to elaborately trigger and simultaneously control the specific metabolic pathways for designed synthesis. To overcome this challenge, the “space-time coupling” strategy for controllable synthesis of quantum dots in live cells has been developed since 2009. By delicately coupling of intracellular selenite reduction metabolism and detoxification of heavy metal ions, quantum dots with different components and tunable sizes can be synthesized. This review focuses on the synthetic regulation, mechanism and biological applications of quantum dots in situ synthesized in live cells by the “space-time coupling” strategy. Subsequently, cell-free quasi-biological systems that are inspired by the live-cell synthesis and constructed by mimetic intracellular biochemical reaction pathways are briefly presented. Finally, challenges and prospects of this strategy are discussed. In the future, with more in-depth research on metabolomics, we believe that in addition to quantum dots, various inorganic nanomaterials with hierarchical structures and multifunction properties can be produced in live cells on purpose by elaborately coupling multiple metabolic pathways, which provides a new insight to synthetic biology.

Key words: quantum dots, live cell, synthesis, metabolism, regulation

中图分类号:

Q 591.1

贾剑红, 杨玲玲, 刘安安, 庞代文. “时-空耦合”活细胞合成量子点[J]. 合成生物学, 2022, 3(2): 385-398.

Jianhong JIA, Lingling YANG, An’an LIU, Daiwen PANG. Space-time-coupled live-cell synthesis of quantum dots[J]. Synthetic Biology Journal, 2022, 3(2): 385-398.

图/表 5

图1 酵母细胞内CdSe量子点的活细胞合成途径及相关机理研究［38，56］

Fig. 1 Biosynthesis pathway for CdSe quantum dots in yeast cells and related mechanisms [38,56]

图2 细胞信标构建生物检测探针的原理及其应用［39］

Fig. 2 Principle and application of constructing biological detection probes by cell beacons[39]

图3 通过MCF-7胞内合成荧光量子点一步标记微囊泡的示意图［40］

Fig. 3 Schematic illustration for one-step labeling of microvesicles by coupling the intracellular synthesis of fluorescent quantum dots in live MCF-7 cells[40]

图4 热醋穆尔氏菌-CdS的反应示意图［61］

Fig. 4 Reaction schematics for the M. thermoacetica-CdS system [61]

图5 准生物体系可控合成纳米材料及应用［70，74］

Fig. 5 Controllable synthesis and application of nanomaterials in quasi-biological systems[70,74]

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“时-空耦合”活细胞合成量子点

Space-time-coupled live-cell synthesis of quantum dots

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