In this work, we develop methodologies for analyzing and cross comparing metabolic models. We investigate three important metabolic networks to discuss the complexity of biological organization of organisms, modeling, and system properties. In particular, we analyze these metabolic networks because of their biotechnological and basic science importance: the photosynthetic carbon metabolism in a general leaf, the Rhodobacter spheroides bacterium, and the Chlamydomonas reinhardtii alga. We adopt single- and multi-objective optimization algorithms to maximize the CO 2 uptake rate and the production of metabolites of industrial interest or for ecological purposes. We focus both on the level of genes (e.g., finding genetic manipulations to increase the production of one or more metabolites) and on finding concentration enzymes for improving the CO 2 consumption. We find that R. spheroides is able to absorb an amount of CO 2 until 57.452 mmol h (-1) gDW (-1) , while C. reinhardtii obtains a maximum of 6.7331. We report that the Pareto front analysis proves extremely useful to compare different organisms, as well as providing the possibility to investigate them with the same framework. By using the sensitivity and robustness analysis, our framework identifies the most sensitive and fragile components of the biological systems we take into account, allowing us to compare their models. We adopt the identifiability analysis to detect functional relations among enzymes; we observe that RuBisCO, GAPDH, and FBPase belong to the same functional group, as suggested also by the sensitivity analysis.

译文

:在这项工作中,我们开发了用于分析和交叉比较代谢模型的方法。我们研究了三个重要的代谢网络,以讨论生物的生物组织,建模和系统特性的复杂性。特别是,由于它们的生物技术和基础科学重要性,我们分析了这些代谢网络:普通叶片,球形红球菌和莱茵衣藻中的光合作用碳代谢。我们采用单目标和多目标优化算法,以最大程度地提高CO 2吸收率和具有工业价值或出于生态目的的代谢产物的生产。我们既关注基因的水平(例如,寻找基因操纵以增加一种或多种代谢产物的产生),又关注于寻找可提高CO 2消耗量的浓缩酶。我们发现R.spheroides能够吸收一定量的CO 2直至57.452 mmol h(-1)gDW(-1),而莱茵衣藻最大吸收量为6.7331。我们报告说,帕累托阵线分析被证明对比较不同的生物非常有用,并且提供了使用相同框架进行研究的可能性。通过使用敏感性和鲁棒性分析,我们的框架可以确定我们所考虑的生物系统中最敏感和最脆弱的组成部分,从而使我们能够比较它们的模型。我们采用可识别性分析来检测酶之间的功能关系;我们观察到RuBisCO,GAPDH和FBPase属于相同的官能团,敏感性分析也表明这一点。

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