Bacterial co-culture with cell signaling translator and growth controller modules for autonomously regulated culture composition
Bacterial co-culture with cell signaling translator and growth controller modules for autonomously regulated culture composition
复制标题
用于自主调节培养物组成的具有细胞信号传导翻译子和生长控制子模块的细菌共培养
DOI：
10.1038/s41467-019-12027-6
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发表时间：
2019-09-11
影响因子：
16.6
通讯作者：
Bentley, William E.
中科院分区：
文献类型：
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作者：
Stephens, Kristina;Pozo, Maria;Bentley, William E.
合成生物学和代谢工程学扩大了以细胞为基础的工程系统的可能性。然而，非天然生物合成和调节成分的添加会使重编程细胞负担过重。为了避免代谢超载，一个新兴的关注领域是工程联盟，其中细胞亚群一起工作来执行所需的功能。这种策略需要对细胞群进行调控。在这里，我们设计了一个合成共培养控制器，由基于细胞的信号转换器和生长控制器模块组成，当实现时，提供对联盟组成的自主调节。该系统采用细菌群体感应（QS）的正交自诱导剂Al-1和Al-2细胞-细胞信号机制，实现菌株间的串扰，并通过QS信号控制生长速率控制器来调节相对种群密度。我们进一步开发了一个简单的数学模型，使细胞和系统设计能够对种群轨迹进行自主闭环控制。
Synthetic biology and metabolic engineering have expanded the possibilities for engineered cell-based systems. The addition of non-native biosynthetic and regulatory components can, however, overburden the reprogrammed cells. In order to avoid metabolic overload, an emerging area of focus is on engineering consortia, wherein cell subpopulations work together to carry out a desired function. This strategy requires regulation of the cell populations. Here, we design a synthetic co-culture controller consisting of cell-based signal translator and growth-controller modules that, when implemented, provide for autonomous regulation of the consortia composition. The system co-opts the orthogonal autoinducer Al-1 and Al-2 cell-cell signaling mechanisms of bacterial quorum sensing (QS) to enable crosstalk between strains and a QS signal-controlled growth rate controller to modulate relative population densities. We further develop a simple mathematical model that enables cell and system design for autonomous closed-loop control of population trajectories.