Abstract:

In synthetic biology, gene modules are fundamental components that facilitate the execution of various biological functions. "Modularity" refers to the property where known genetic elements maintain their relatively independent function after being assembled into a specific gene circuit. Unlike traditional engineering systems, which often possess independent and stable characteristics, gene circuits must navigate the complexities of dynamically fluctuating cellular environments. This inherent variability means that the effectiveness of gene circuits in producing functional proteins is highly contingent upon the availability of intracellular resources. When these resources are scarce, it can create significant bottlenecks that impede the overall functionality of the gene circuits. Moreover, gene modules do not typically operate in isolation; rather, they are integrated into complex network systems that interact with other modules to achieve multifaceted regulatory objectives. This interconnectedness leads to competition among various modules for limited intracellular resources, which disrupts the basic principle of modular design. Restoring the modularity of gene circuits is crucial for constructing universal theoretical models of life systems, which can further promote the intelligent development of artificial life systems. Recently, an increasing number of studies have focused on how this resource competition impacts the performance of gene circuits. These investigations have deepened our understanding of the underlying mechanisms at play and have paved the way for optimizing gene circuit designs to enhance their modularity and functionality. This review aims to introduce the influence of cellular resource competition on gene circuit function. It will explore various aspects, including the fluctuations in noise levels within gene circuits, the coupling relationships among different gene modules, and the emergent "winner-takes-all" phenomenon. Additionally, we summarize existing strategies for controlling these challenges, such as the orthogonal design of cellular resources, the regulation of single gene modules, and the coordinated control of multiple gene modules. With the rapid development of synthetic biology, artificially designed gene circuits are becoming increasingly complex in both structure and function. This trend suggests that future research will no longer be limited to simple resource competition control systems but will need to expand to larger-scale research areas. At the same time, research directions should extend from basic research to practical applications, ultimately aiming to construct precisely controllable artificial life systems.

Key words: synthetic biology, genetic parts, resource competition, modularity, design strategies

摘要：

在合成生物学中，基因模块是执行生物功能的核心元件。“模块性”是指已知基因元件在被拼装为目的基因回路后仍能保持其功能相对独立的特性。不同于传统工程学独立且稳定的特性，基因回路存在于动态变化的细胞环境中，其功能蛋白的表达效率高度依赖于胞内资源。有限的资源分配使得基因回路面临胞内资源的约束挑战，导致基因回路的模块性丧失。恢复基因回路的模块性有助于构建普适的生命系统理论模型，从而推动人工生命体系的智能化发展。近年来，有关资源竞争如何重塑基因回路表现的研究逐渐增多，这些研究加深了对潜在作用机制的理解，并推动了基因回路设计的优化。本综述系统阐述了细胞资源竞争现象对基因回路功能的影响，包括基因回路噪音的改变，基因模块的耦合关系，以及赢者通吃的涌现性。同时，对现有控制策略进行了全面归纳，包括细胞资源的正交化设计，单基因模块的资源调控以及多基因模块的统筹化控制。随着合成生物学的快速发展，人工设计的基因回路在结构和功能上会变得更加复杂。这一趋势预示着未来的研究重点将不再局限于简单的资源竞争控制体系，而需要向更大规模的研究范畴拓展。与此同时，研究方向应从基础研究探索延伸至实际应用，最终实现精确可控的人工生命体系的构建。

关键词: 合成生物学, 基因元件, 资源竞争, 模块化, 设计策略