A modular minimal cell model: Purine and pyrimidine transport and metabolism
A modular minimal cell model: Purine and pyrimidine transport and metabolism
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DOI：
10.1073/pnas.0400962101
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发表时间：
2004-04-27
影响因子：
11.1
通讯作者：
Shuler, ML
中科院分区：
文献类型：
--
作者：
Castellanos, M;Wilson, DB;Shuler, ML
需要更全面地了解细胞生理学与基因组结构的关系。由于生物有机体固有的复杂性，只有最简单的细胞才能完整定义所有组件及其相互作用。最小细胞的理论和实验构建已被建议作为发展这种理解的工具。我们的最终目标是将大肠杆菌的“粗粒度”集总参数计算机模型转换为“最小细胞”的遗传和化学详细模型。基础大肠杆菌模型已转换为异养细菌的通用模型。这种粗粒最小细胞模型在功能上是完整的，生长速率、组成、分裂和细胞形态的变化是动态模拟的自然输出，其中仅指定了细胞和培养基的初始组成。粗粒度模型使用伪化学物质（或模块），它们是具有相似化学和代谢动力学的不同化学物质的聚合体。该模型提供了一个框架，其中这些模块可以“分解”为化学和遗传描述，同时保持与所有其他功能元素的连接。在这里，我们证明了核苷酸前体转运和代谢的详细描述已成功整合到全细胞模型中。与最小细胞中的其他理论预测相比，该核苷酸子模型需要更少的 (12) 个基因。模块化的证明表明可以并行开发模块并将它们重新组合成原核细胞的功能齐全的化学和遗传详细模型。
A more complete understanding of the relationship of cell physiology to genomic structure is desirable. Because of the intrinsic complexity of biological organisms, only the simplest cells will allow complete definition of all components and their interactions. The theoretical and experimental construction of a minimal cell has been suggested as a tool to develop such an understanding. Our ultimate goal is to convert a "coarse-grain" lumped parameter computer model of Escherichia coli into a genetically and chemically detailed model of a "minimal cell." The base E. coli model has been converted into a generalized model of a heterotrophic bacterium. This coarse-grain minimal cell model is functionally complete, with growth rate, composition, division, and changes in cell morphology as natural outputs from dynamic simulations where only the initial composition of the cell and of the medium are specified. A coarse-grain model uses pseudochemical species (or modules) that are aggregates of distinct chemical species that share similar chemistry and metabolic dynamics. This model provides a framework in which these modules can be "delumped" into chemical and genetic descriptions while maintaining connectivity to all other functional elements. Here we demonstrate that a detailed description of nucleotide precursors transport and metabolism is successfully integrated into the whole-cell model. This nucleotide submodel requires fewer (12) genes than other theoretical predictions in minimal cells. The demonstration of modularity suggests the possibility of developing modules in parallel and recombining them into a fully functional chemically and genetically detailed model of a prokaryote cell.