Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.
Imperial College Centre for Synthetic Biology (IC-CSynB), Imperial College London, London, SW7 2AZ, UK.
Nat Commun. 2018 Jul 11;9(1):2677. doi: 10.1038/s41467-018-05046-2.
Advancing synthetic biology to the multicellular level requires the development of multiple cell-to-cell communication channels that propagate information with minimal signal interference. The development of quorum-sensing devices, the cornerstone technology for building microbial communities with coordinated system behaviour, has largely focused on cognate acyl-homoserine lactone (AHL)/transcription factor pairs, while the use of non-cognate pairs as a design feature has received limited attention. Here, we demonstrate a large library of AHL-receiver devices, with all cognate and non-cognate chemical signal interactions quantified, and we develop a software tool that automatically selects orthogonal communication channels. We use this approach to identify up to four orthogonal channels in silico, and experimentally demonstrate the simultaneous use of three channels in co-culture. The development of multiple non-interfering cell-to-cell communication channels is an enabling step that facilitates the design of synthetic consortia for applications including distributed bio-computation, increased bioprocess efficiency, cell specialisation and spatial organisation.
将合成生物学推向细胞水平需要开发多种细胞间通信通道，这些通道以最小的信号干扰来传播信息。群体感应装置的发展是构建具有协调系统行为的微生物群落的基石技术，主要集中在同源酰基高丝氨酸内酯 (AHL)/转录因子对上，而将非同源对用作设计特征的应用受到的关注有限。在这里，我们展示了一个大型 AHL 受体设备库，其中所有同源和非同源化学信号相互作用都经过了量化，并且我们开发了一个软件工具，可以自动选择正交通信通道。我们使用这种方法在计算机上识别多达四个正交通道，并在共培养中实验证明了同时使用三个通道。开发多个不干扰的细胞间通信通道是一个可行的步骤，它促进了用于分布式生物计算、提高生物过程效率、细胞专业化和空间组织等应用的合成联合体的设计。
