Systems Biology Department, Centro Nacional de Biotecnologia-CSIC, Campus de Cantoblanco, Madrid, 28049, Spain.
School of Computing, Newcastle University, Newcastle Upon Tyne, NE4 5TG, UK.
Nat Commun. 2021 Jan 13;12(1):355. doi: 10.1038/s41467-020-20656-5.
The implementation of Boolean logic circuits in cells have become a very active field within synthetic biology. Although these are mostly focussed on the genetic components alone, the context in which the circuit performs is crucial for its outcome. We characterise 20 genetic NOT logic gates in up to 7 bacterial-based contexts each, to generate 135 different functions. The contexts we focus on are combinations of four plasmid backbones and three hosts, two Escherichia coli and one Pseudomonas putida strains. Each gate shows seven different dynamic behaviours, depending on the context. That is, gates can be fine-tuned by changing only contextual parameters, thus improving the compatibility between gates. Finally, we analyse portability by measuring, scoring, and comparing gate performance across contexts. Rather than being a limitation, we argue that the effect of the genetic background on synthetic constructs expands functionality, and advocate for considering context as a fundamental design parameter.
在合成生物学中，细胞内布尔逻辑电路的实现已经成为一个非常活跃的领域。尽管这些研究主要集中在遗传元件上，但电路执行的环境对于其结果至关重要。我们在多达 7 种基于细菌的环境中对 20 个遗传 NOT 逻辑门进行了特征描述，以产生 135 种不同的功能。我们关注的环境是四种质粒骨架和三种宿主的组合，其中两种是大肠杆菌，一种是恶臭假单胞菌。每个门都显示出七种不同的动态行为，具体取决于上下文。也就是说，仅通过更改上下文参数就可以对门进行微调，从而提高门之间的兼容性。最后，我们通过在不同上下文中测量、评分和比较门的性能来分析可移植性。我们认为，遗传背景对合成结构的影响不是限制，而是扩展了功能，并主张将上下文视为基本设计参数。
