La modélisation métabolique est un outil performant pour mieux comprendre, prédire et optimiser les bioprocédés, particulièrement lorsqu'ils impliquent des molécules d'intérêt. Malheureusement, l'utilisation de cette approche de modélisation pour des métabolismes dynamiques est difficile à cause du manque de données expérimentales nécessaires pour définir et calibrer les cinétiques des réactions appartenant aux chemins métaboliques. C'est pourquoi, les modèles métaboliques sont souvent utilisés sous l'hypothèse de croissance équilibrée. Cependant, pour certains procédés comme la croissance photoautotrophique des microalgues, l'hypothèse de croissance équilibrée ne semble pas raisonnable à cause de la synchronisation de leur cycle circadien sur la lumière du jour. Cependant, une compréhension approfondie du métabolisme des microalgues est nécessaire afin d'optimiser les rendements de production des bioprocédés basés sur ces microorganismes, comme par exemple la production de biocarburants.Dans cette thèse, DRUM, une nouvelle approche de modélisation métabolique dynamique qui prend en compte la croissance non-équilibrée, a été développée. La première étape de l'approche consiste à découper le réseau métabolique en sous-réseaux décrivant des réactions qui sont spatialement et fonctionnellement proches et supposés satisfaire une croissance équilibrée. Les métabolites interconnectant les sous-réseaux peuvent alors avoir un comportement dynamique. Puis, grâce à l'analyse de modes élémentaires, chaque sous-réseau est réduit à des réactions macroscopiques, pour lesquelles des cinétiques simples sont supposées. Enfin, un système d'équations ordinaires différentielles est obtenu pour décrire la consommation des substrats, la production de biomasse, les produits excrétés et l'accumulation de certains métabolites intracellulaires.DRUM a été appliquée à l'accumulation des lipides et des carbohydrates de la microalgue Tisochrysis lutea soumise à des cycles jour/nuits en condition d'azote normal et de carence azotée. Le model décrit avec précision les données expérimentales. DRUM a également été appliquée à la microalgue Chlorella Sorokiniana en croissance hétérotrophique, montrant que la croissance équilibrée est valide dans ce cas-là. / Metabolic modeling is a powerful tool to understand, predict and optimize bioprocesses, particularly when they imply intracellular molecules of interest. Unfortunately, the use of metabolic models for time varying metabolic fluxes is hampered by the lack of experimental data required to define and calibrate the kinetic reaction rates of the metabolic pathways. For this reason, metabolic models are often used under the balanced growth hypothesis. However, for some processes such as the photoautotrophic metabolism of microalgae, the balanced-growth assumption appears to be unreasonable because of the synchronization of their circadian cycle on the daily light. Yet, understanding microalgae metabolism is necessary to optimize the production yield of bioprocesses based on this microorganism, as for example production of third-generation biofuels.In this PhD thesis, DRUM, a new dynamic metabolic modeling framework that handles the non-balanced growth condition and hence accumulation of intracellular metabolites was developed. The first stage of the approach consists in splitting the metabolic network into sub-networks describing reactions which are spatially and functionally close, and which are assumed to satisfy balanced growth condition. The left metabolites interconnecting the sub-networks behave dynamically. Then, thanks to Elementary Flux Mode analysis, each sub-network is reduced to macroscopic reactions, for which simple kinetics are assumed. Finally, an Ordinary Differential Equation system is obtained to describe substrate consumption, biomass production, products excretion and accumulation of some internal metabolites.DRUM was applied to the accumulation of lipids and carbohydrates of the microalgae Tisochrysis lutea under day/night cycles in normal and nitrogen starvation conditions. The resulting model describes accurately experimental data. It efficiently predicts the accumulation and consumption of lipids and carbohydrates. DRUM was also applied to the microalgae Chlorella Sorokiniana in dark heterotrophic growth, showing that the balanced-growth assumption was valid in this case.

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Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A presente tese à composta por trÃs capÃtulos. O primeiro capÃtulo aplica o teste de quebra estrutural de Bai e Perron (1998, 2003) para analisar as mudanÃas na conduÃÃo da polÃtica monetÃria brasileira durante o perÃodo de 2002 â 2013. Estimamos uma regra de Taylor forward-looking, a partir da metodologia proposta por Clarida et. al. (1999) e Conrad e Eife (2012) e uma meta de inflaÃÃo implÃcita com base nos dados e nos parÃmetros estimados da regra de Taylor. Os resultados indicaram a existÃncia de trÃs quebras estruturais nos parÃmetros estimados da regra de Taylor, a primeira no ano de 2005, a segunda em 2008 e a Ãltima em 2011, evidenciando uma mudanÃa na conduta da polÃtica monetÃria. Observamos que a polÃtica monetÃria foi utilizada como instrumento para estabilizar o produto, mas o BACEN vem dando uma maior importÃncia ao hiato do produto nos Ãltimos anos. No segundo capÃtulo aplica-se uma decomposiÃÃo tendÃncia e ciclo multivariado aos setores da economia brasileira, focando a anÃlise nas relaÃÃes entre os setores e na dataÃÃo dos ciclos de negÃcios individuais. Utilizamos uma base de dados trimestrais composta pelo Produto Interno Bruto - PIB de cada setor, entre os anos de 1995 e 2013. Os resultados confirmam a existÃncia de uma relaÃÃo de equilÃbrio de curto e longo prazo entre os setores e uma alta correlaÃÃo entre as tendÃncias setoriais. No terceiro capÃtulo testamos se um modelo neoclÃssico bÃsico poderia explicar as flutuaÃÃes macroeconÃmicas do consumo, investimento e produto per capita brasileiro entre 1991 e 2013. Utilizamos um arcabouÃo teÃrico à fundamentado no modelo de crescimento neoclÃssico estocÃstico proposto por King et. al. (1988a, 1988b) e King et. al. (1991). As evidÃncias empÃricas estÃo de acordo com as suposiÃÃes teÃricas do modelo. As variÃveis apresentam um comportamento de passeio aleatÃrio e existe um equilÃbrio de longo prazo entre elas, apontando uma relaÃÃo de estacionaridade entre consumo â produto e investimento â produto. A hipÃtese de crescimento balanceado entre as variÃveis foi verificada e representam um impacto positivo, significativo e de mesma magnitude sobre as variÃveis. / This thesis consists of three chapters. The first chapter applies the structural break of Bai and Perron (1998, 2003) test to analyze changes in the conduction of monetary policy during the period 2002-2013. Estimate a Taylor rule forward-looking, based on the methodology proposed by Clarida et. al. (1999) and Conrad and Eife (2012) and a target headline inflation based on the data and the estimated parameters of the Taylor rule. The results indicated the existence of three structural breaks in the estimated parameters of the Taylor rule, the first in 2005, second in 2008 and the last in 2011, indicating a change in the conduct of monetary policy. We observed that monetary policy was used as a tool to stabilize the product, but the Brazilian Central Bank has been giving less importance to the output gap in recent years. The second chapter applies a decomposition multivariate trend and cycle sectors of the Brazilian economy, focusing the analysis on the relations between the sectors and the dating of individual business cycles. We use a database of quarterly data for Gross Domestic Product - GDP of each sector, between years 1995-2013 The results confirm the existence of short and long term equilibrium among sectors and a high correlation between trends sector. In the third chapter we test whether a basic neoclassical model could explain Brazilian macroeconomic fluctuations in consumption, investment and product per capita between 1991-2013. We use a theoretical framework based on the stochastic neoclassical growth model proposed by King et. al. (1988a, 1988b) and King et. al. (1991). Empirical evidence is consistent with the theoretical assumptions of the model. The variables present behavior of random walk and there is a long-term equilibrium between them, pointing a stationary relationship between consumption - output and investment - product. The hypothesis of balanced growth between variables was checked and represent a positive, significant and of the same magnitude impact on the variables.