The current investigation is aimed at the reconstruction and analysis of genome-scale metabolic models. Specifically, it is focused on the use of mathematical-computational simulations to predict the cellular metabolism behavior towards bio-products production. The photosynthetic cyanobacterium Synechococcus elongatus PCC7942 was studied as biological system. This prokaryotic has been used in several studies as a biological platform for the synthesis of several substances for industrial interest. These studies are based on the advantage of autotrophic systems, which basically requires light and CO2 for growth. The main objective of this thesis is the integration of different types of biological information, whose interaction can be extract applicable knowledge for economic interests. To this end, our study was addressed to the use of methods for modeling, analyzing and predicting the behavior of metabolic phenotypes of cyanobacterium. The work has been divided into chapters organized sequentially, where the starting point was the in silico metabolic reconstruction network. This process intent to join in a metabolic model of all chemical reactions codified in genome. The stoichiometric coefficients of each reactions, can be arranged into a sparse matrix (stoichiometric matrix), where the columns corresponds to reactions and rows to metabolites. As a result of this process the first model was obtained (iSyf646) than later was updated to another (iSyf714). Both were generated from data ¿omics published in databases, scientific reviews as well as textbooks. To validate them, each one of the stoichiometric matrix together with relevant constraints were used by simulation techniques based on linear programming. These reconstructions have to be flexible enough to allow autotrophic growth under which the organism grows in nature. Once the reconstructions were validated, environmental variations can be simulated and we were able to study its effects through changes in outline system parameters. Subsequently, synthetic capabilities were evaluated from the in silico models in order to design metabolic engineering strategies. To do this a genetic variation was simulated in reactions network, where the disturbed stoichiometric matrix was the object of the quadratic optimization methods. As a results sets of optimal solutions were generated to enhanced production of various metabolites of energetic interest such as: ethanol, n-butanol isomers, lipids and hydrogen, as well as lactic acid as the compound which is an interest to the industry. Furthermore, functionally coupled reactions have been studied and have been weighted to the importance in the production of metabolites. Finally, genome-scale metabolic models allow us to establish criteria to integrate different types of data to help of find important points of regulation that may be subject to genetic modification. These regulatory centers have been investigated under drastic changes of illumination and have been inferred operational principles of cyanobacterium metabolism. In general, this thesis presents the metabolic capabilities of photosynthetic cyanobacterium Synechococcus elongatus PCC7942 to produce substances of interest, being a potential biological platform for clean and sustainable production. / Triana Dopico, J. (2014). Model-based analysis and metabolic design of a cyanobacterium for bio-products synthesis [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/39351 / TESIS

I den här studien utformas och implementeras en prototyp av ett automatiskt grafritningsverktyg. Under processen analyseras och evalueras flera välkända och viktiga algoritmer. Algoritmen som används i prototypen modifieras och förbättras för att uppfylla företaget FindOuts speciella krav. Dessutom strävar vi efter att hitta förbättringar med avseende på visualisering och prestanda för algoritmer genom att studera aktuella arbeten. Genom litteraturoch empiriska studier, drar vi slutsatsen att Sugiyama-ramverket passar bäst för hierarkiska och liknande grafer. Den genererade grafritningen är stabil, läsbar och följer de flesta estetiska kriterier. Dessutom används kraftbaserad layout för att placera de icke sammanhängande delgraferna på lämpliga positioner. Attraktionsoch repulsionskraft mellan delgrafer gör att hela grafen blir kompakt utan överlappning, vilket är ett av företagets krav. Några problem såsom att lägga till nya noder och kanter är inte helt lösta på grund av konflikten mellan estetiska kriterier och användarkrav. Vi anser att en algoritm baserad på användarkrav är lämplig att integreras i en nästa generation av vår prototyp. En del av heuristiken kan också förbättras. Vi presenterar möjliga lösningar och föreslår att en noggrann jämförelse mellan olika algoritmer bör tas upp i framtida arbete. / A prototype of an automatic graph drawing tool was designed and implemented in this thesis project. In this process various well-known and important algorithms were analyzed and evaluated. Algorithms applied in the prototype were modified and improved to fulfill FindOut’s special requirements. Besides this, a pursuit of an improvement on visualizations and performance of algorithms was conducted by studying the latest research works. Through these theoretical and empirical studies, we concluded that the Sugiyama framework is the most suitable algorithm to generate the workflow type of graph. The generated graphs are stable, readable and follows most aesthetic standards. Furthermore, force-directed algorithms were utilized to put graphs at appropriate positions. The attraction and repulsion force between sub-graphs can make the whole graph compact without overlapping, which fulfills the company’s requirement. However some of the problems, such as importing new nodes and edges, have not been perfectly resolved due to the conflict between the aesthetic and user requirements. Thus we think that a user-constraints based algorithm is suitable to be integrated into our next generation prototype. Some of the heuristics also have room for improvement. We discussed the possible solutions and suggested that a comparative study of different algorithms should be included in the future work.