Journal
ACS SYNTHETIC BIOLOGY
Volume 2, Issue 5, Pages 274-288Publisher
AMER CHEMICAL SOC
DOI: 10.1021/sb300102k
Keywords
metabolic CAD; synthetic biology; multi-objective optimization; sensitivity analysis; robustness analysis; photosynthetic yield
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Funding
- European Commission - Capacities Area - Research Infrastructures
- [1220]
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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 CO2 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 CO2 consumption. We find that R. spheroides is able to absorb an amount of CO2 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.
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