Krishnan J, Lu Lingjun, Alam Nazki Aiman
Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Institute for Systems and Synthetic Biology, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
J R Soc Interface. 2020 May;17(166):20200251. doi: 10.1098/rsif.2020.0251. Epub 2020 May 27.
Biochemical pathways and networks are central to cellular information processing. While a broad range of studies have dissected multiple aspects of information processing in biochemical pathways, the effect of spatial organization remains much less understood. It is clear that space is central to intracellular organization, plays important roles in cellular information processing and has been exploited in evolution; additionally, it is being increasingly exploited in synthetic biology through the development of artificial compartments, in a variety of ways. In this paper, we dissect different aspects of the interplay between spatial organization and biochemical pathways, by focusing on basic building blocks of these pathways: covalent modification cycles and two-component systems, with enzymes which may be monofunctional or bifunctional. Our analysis of spatial organization is performed by examining a range of 'spatial designs': patterns of localization or non-localization of enzymes/substrates, theoretically and computationally. Using these well-characterized systems, we analyse the following. (i) The effect of different types of spatial organization on the overall kinetics of modification, and the role of distinct modification mechanisms therein. (ii) How different information processing characteristics seen experimentally and studied from the viewpoint of kinetics are perturbed, or generated. (iii) How the activity of enzymes (bifunctional enzymes in particular) may be spatially manipulated, and the relationship between localization and activity. (iv) How transitions in spatial organization (encountered either through evolution or through the lifetime of cells, as seen in multiple model organisms) impacts the kinetic module (and pathway) behaviour, and how transitions in chemistry may be impacted by prior spatial organization. The basic insights which emerge are central to understanding the role of spatial organization in biochemical pathways in both bacteria and eukaryotes, and are of direct relevance to engineering spatial organization of pathways in bottom-up synthetic biology in cellular and cell-free systems.
生化途径和网络是细胞信息处理的核心。虽然广泛的研究剖析了生化途径中信息处理的多个方面，但空间组织的影响仍知之甚少。很明显，空间是细胞内组织的核心，在细胞信息处理中发挥着重要作用，并且在进化过程中已被利用；此外，通过人工隔室的开发，它在合成生物学中正以各种方式越来越多地被利用。在本文中，我们通过关注这些途径的基本组成部分：共价修饰循环和双组分系统，以及可能是单功能或双功能的酶，来剖析空间组织与生化途径之间相互作用的不同方面。我们通过在理论和计算上检查一系列“空间设计”：酶/底物的定位或非定位模式，来进行空间组织分析。使用这些特征明确的系统，我们分析以下内容。（i）不同类型的空间组织对修饰总体动力学的影响，以及其中不同修饰机制的作用。（ii）从动力学角度实验观察和研究的不同信息处理特征是如何受到干扰或产生的。（iii）酶（特别是双功能酶）的活性如何在空间上被操纵，以及定位与活性之间的关系。（iv）空间组织的转变（如在多种模式生物中通过进化或细胞寿命所遇到的）如何影响动力学模块（和途径）行为，以及化学转变如何受到先前空间组织的影响。所获得的基本见解对于理解细菌和真核生物中空间组织在生化途径中的作用至关重要，并且与在细胞和无细胞系统中自下而上的合成生物学中途径的工程化空间组织直接相关。
