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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A modular minimal cell model: Purine and pyrimidine transport and metabolism
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A modular minimal cell model: Purine and pyrimidine transport and metabolism

机译：模块化最小细胞模型：嘌呤和嘧啶的转运和代谢

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摘要

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.
机译：需要对细胞生理学与基因组结构的关系有更完整的了解。由于生物有机体的内在复杂性，只有最简单的细胞才能完整定义所有组分及其相互作用。已经提出了最小单元的理论和实验构造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”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。基本的大肠杆菌模型已转换为异养细菌的通用模型。这种粗粒度的最小细胞模型在功能上是完整的，其生长速率，组成，分裂和细胞形态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。粗粒模型使用伪化学物质（或模块），这些化学物质是具有相似化学和代谢动力学特性的不同化学物质的集合。该模型提供了一个框架，在其中可以将这些模块“放入”化学和遗传描述中，同时保持与所有其他功能元件的连通性。在这里，我们证明了核苷酸前体运输和代谢的详细描述已成功整合到全细胞模型中。在最小细胞中，该核苷酸亚模型比其他理论预测所需的基因更少（12）。模块化的演示表明，有可能并行开发模块并将其重组为原核生物细胞的功能全面的化学和遗传详细模型。

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