合成生物学 ›› 2021, Vol. 2 ›› Issue (2): 234-246.DOI: 10.12211/2096-8280.2020-066
周爱林1,2, 刘奕1, 巴方1, 钟超1,3,4
收稿日期:
2020-06-05
修回日期:
2021-02-19
出版日期:
2021-04-30
发布日期:
2021-04-30
通讯作者:
钟超
作者简介:
基金资助:
ZHOU Ailin1,2, LIU Yi1, BA Fang1, ZHONG Chao1,3,4
Received:
2020-06-05
Revised:
2021-02-19
Online:
2021-04-30
Published:
2021-04-30
Contact:
ZHONG Chao
摘要:
群体感应现象指的是微生物通过独特的交流方式使不同菌个体间的行为同步,从而展现群体性行为。当前在微生物群体感应系统方面的研究,除了促进或抑制天然群体感应方面的基础研究外,研究人员逐渐开始将群体感应系统引入到合成生物学的工程应用研究,并且将其广泛运用在医学、工业、环境等应用领域。本文主要总结了细菌群体感应元件在构建过程中的常用策略与方法,并探讨了基于群体感应基因元件改造的工程菌在动态代谢调节、周期性振荡呈现、异种菌种间关系的构建等方面的应用。 群体感应元件的研究主要包括新群体感应元件的开发和针对已有群体感应元件的优化。通过模拟、优化群体感应元件并将其模块化,研究人员构建了丰富的群体感应基因元件库,使群体感应能被灵活应用于不同场景。另外,通过在细菌中引入群体感应基因回路,可以将单个细菌内部的各类反馈回路较好地拓展到整个细菌群体中,而这种多细胞体系的构建,使得更多复杂的功能得以实现,如通过群体感应实现动态代谢调节从而提高发酵效率,或实现群体周期性振荡以释放肿瘤杀伤药物等。此外,环境中异种微生物的关系也可以通过外源引入群体感应来进行调控,这为微生物的共培养提供了新工具,更为复杂的合成生物学系统的建立提供了新思路。随着机器学习等计算机领域的发展,未来可以更多借助计算机来设计复杂群体感应回路,并对外源群体感应引入后的效果做出更精准的预测。
中图分类号:
周爱林, 刘奕, 巴方, 钟超. 细菌群体感应元件构建和工程应用[J]. 合成生物学, 2021, 2(2): 234-246.
ZHOU Ailin, LIU Yi, BA Fang, ZHONG Chao. Construction and engineering application of bacterial quorum sensing elements[J]. Synthetic Biology Journal, 2021, 2(2): 234-246.
项目 | 化学诱导剂 | 群体感应 |
---|---|---|
可控性 | 较好 可以人为通过加入化学诱导剂,较为精确地控制基因表达的时间 | 较好 群体感应的基因表达开启与否本来由元件内源参数决定,除了在使用前改造元件、调整内源参数,还可以将群体感应中自体诱导物的启动子替换为外源分子调控的诱导型启动子,通过外加特定的诱导物实现对群体感应行为的控制[ |
动态性 | 较差 需要实时检测细胞生长状况,并在合适的时机添加诱导剂 | 较好 群体数量实时决定群体行为 |
可逆性 | 较差 一经添加便会一直存在于介质中,只能起到单次控制的效果[ | 较差,但可以优化 Miano等[ |
经济性 | 较差 现常用的化学诱导剂如IPTG等成本较高[ | 较好 只在最初基因回路构建上存在一次性成本 |
表1 化学诱导与群体感应在代谢调控中应用的对比[23-24,26,39-40]
Tab. 1 Comparison between chemical inducers and quorum sensing on their application in metabolic regulation[23-24,26,39-40]
项目 | 化学诱导剂 | 群体感应 |
---|---|---|
可控性 | 较好 可以人为通过加入化学诱导剂,较为精确地控制基因表达的时间 | 较好 群体感应的基因表达开启与否本来由元件内源参数决定,除了在使用前改造元件、调整内源参数,还可以将群体感应中自体诱导物的启动子替换为外源分子调控的诱导型启动子,通过外加特定的诱导物实现对群体感应行为的控制[ |
动态性 | 较差 需要实时检测细胞生长状况,并在合适的时机添加诱导剂 | 较好 群体数量实时决定群体行为 |
可逆性 | 较差 一经添加便会一直存在于介质中,只能起到单次控制的效果[ | 较差,但可以优化 Miano等[ |
经济性 | 较差 现常用的化学诱导剂如IPTG等成本较高[ | 较好 只在最初基因回路构建上存在一次性成本 |
图4 三种典型思路用于构建多细胞振荡体系[30, 56-57][(a),(b),(c)分别对应三种振荡回路与群体感应结合的思路;(d)利用群体感应形成规律图案[基于思路二构建的系统,通过群体感应,自体诱导物AHL的浓度周期性到达阈值,而菌落边缘的细菌有更强的基因表达能力(表达荧光蛋白),两者构成AND逻辑门,使菌落呈现出规律的图案];(e)实现更大范围群体周期性行为的同步;(f)利用群体感应实现的震荡系统治疗癌症]
Fig. 4 Three strategies for construcling multicellular oscillation systems[30, 56-57][(a), (b) and (c) refers to each of the three strategies for combining oscillation circuit with quorum sensing.(d)Forming regular pattern using QS.By using method B, autoinducer concentration periodically reaches the threshold. Since only bacteria at the edge of the colony have higher gene expression (like the expression of fluorescent protein),an AND logic gate is constructed to make the colony show rhythmic pattern.(e)Realization of the collective oscillation in a bigger range.(f)Employment of QS oscillation system in cancer treatment]
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