Toward predictable universal genetic circuit design

Synthetic biologists have applied systematic engineering principles to genetic circuit design to devise biological systems with bespoke behaviors, such as Boolean logic gates, signal filters, and oscillators. While the scope of these achievements has been confined to a few model organisms (e.g., E. coli), non-model organisms might play a more important role in real-world applications due to unique metabolisms and adaptations for specific environments. Therefore, transferring the genetic parts and tools to non‐model organisms is crucial for transforming genetic circuits from laboratory to the field. 

Recently, Quantitative Biology published a commentary entitled “Toward predictable universal genetic circuit design”, which reviews the host contexts hindering the predictable transplantation of genetic circuits, current strategies for designing universal genetic circuits, and future directions of universal genetic circuit design.

The regulatory modalities developed in model chassis cannot be readily ported into a new chassis with their initial functionality, as they must adapt to host‐specific gene expression machinery, metabolism, and the DNA vectors used to encode the genetic circuits (Figure 1A). Therefore, a universal genetic circuit needs to comprise several modules: a power supply module that encodes heterologous gene expression machinery orthogonal to host machinery; a processor module that programs the input-output relationship for precise control of target gene expression; a controller module that decouples synthetic circuits from variations in host contexts (Figure 1B). In the future, expanding the regulatory toolbox, establishing standardized workflows to characterize the universal parts, integrating computer-aided design tools, and developing high‐throughput experimental pipelines will enable automatic design and effortless optimization of universal circuits to program non‐model organisms for delivering fieldable technologies and real‐world products.