Biological Design Principles of Complex Feedback Modules in the E.coli Ammonia Assimilation System
Biological Design Principles of Complex Feedback Modules in the E.coli Ammonia Assimilation System
复制标题
大肠杆菌氨同化系统中复杂反馈模块的生物学设计原理
DOI：
10.1162/artl_a_00049
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发表时间：
2012
期刊：
影响因子：
2.6
通讯作者：
Hiroyuki Kurata
中科院分区：
文献类型：
--
作者：
Koichi Masaki;Kazuhiro Maeda;Hiroyuki Kurata
为了合成自然或人造生命，与工程系统相比，了解生化网络如何产生特定细胞功能并进化复杂系统的设计原理至关重要。面对环境和遗传变异引起的扰动，细胞系统仍能保持稳健性。与控制工程架构类似，单元内模块化结构的复杂性可归因于实现鲁棒性的必要性。为了揭示这种生物设计，E.分析了大肠杆菌氨同化系统，该系统由复杂但高度结构化的模块组成：具有催化可逆反应的双功能酶级联的谷氨酰胺合成酶（GS）活性反馈控制模块，以及具有正反馈环和负反馈环的GS合成反馈控制模块。我们开发了一个统一这两个模块的全尺寸动态模型，并分析了其针对内部和外部扰动的鲁棒性和微调。 GS 活性控制被添加到 GS 合成模块中，以改善其对氨消耗的瞬态响应，补偿每个模块的权衡，但其对内部扰动的鲁棒性丢失。这些发现提出了生命合成所必需的一些设计原则。
To synthesize natural or artificial life, it is critically important to understand the design principles of how biochemical networks generate particular cellular functions and evolve complex systems in comparison with engineering systems. Cellular systems maintain their robustness in the face of perturbations arising from environmental and genetic variations. In analogy to control engineering architectures, the complexity of modular structures within a cell can be attributed to the necessity of achieving robustness. To reveal such biological design, theE. coliammonia assimilation system is analyzed, which consists of complex but highly structured modules: the glutamine synthetase (GS) activity feedback control module with bifunctional enzyme cascades for catalyzing reversible reactions, and the GS synthesis feedback control module with positive and negative feedback loops. We develop a full-scale dynamic model that unifies the two modules, and we analyze its robustness and fine tuning with respect to internal and external perturbations. The GS activity control is added to the GS synthesis module to improve its transient response to ammonia depletion, compensating the tradeoffs of each module, but its robustness to internal perturbations is lost. These findings suggest some design principles necessary for the synthesis of life.