Examinando por Materia "Modelado metabólico"

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    Conceptos básicos de análisis de fluxes metabólicos.
    (Universidad del Valle, 2020-11-11) Sánchez Henao, Claudia Patricia; Ramirez Malule, Howard Diego; López Agudelo, Victor Alonso
    El metabolismo representa el nivel biológico que más se relaciona con los fenotipos de la célula y, las alteraciones o reprogramaciones de éste pueden, entre otras, (i) afectar la producción de metabolitos primarios o secundarios en microorganismos de interés biotecnológico, (ii) favorecer o no la inhibición del crecimiento en organismos patógenos y (iii) desarrollar desórdenes metabólicos como la obesidad o la diabetes. Es por ello, que el estudio del metabolismo, el rediseño, y el redireccionamiento de fluxes metabólicos se ha convertido en un área importante de investigación (también conocida como Ingeniería Metabólica), ya que ha permitido el desarrollo y diseño de procesos biológicos mejorados, la identificación de blancos terapéuticos, el diseño de estrategias terapéuticas para curar desordenes metabólicos y la identificación de biomarcadores en cáncer, entre otros. Actualmente, se han desarrollado metodologías computacionales que permiten estudiar el metabolismo celular a diferentes condiciones medioambientales, dirigiendo la experimentación con las predicciones del modelo. El propósito de esta revisión es resaltar la importancia del análisis de fluxes metabólicos como una metodología general para estudiar la reprogramación metabólica en distintos organismos de interés biotecnológico, médico, y terapéutico. Este trabajo condensa las bases teóricas y los conceptos claves para entender el análisis de fluxes metabólicos, lo cual será un insumo fundamental para aquellos que se están adentrando al mundo de la biología de sistemas o áreas afines.
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    Evaluation of metabolic capabilities of Cupriavidus necator to produce polyhydroxyalkanoates using low-cost carbon sources
    (Universidad del Valle, 2026) Ascencio Galván, Martha Ligia; Ramirez-Malule, Howard; López Agudelo, Víctor Alonso; Gómez Ríos, David
    Cupriavidus necator (C. necator) is a bacterium of great biotechnological interest due to its ability to synthesize polyhydroxyalkanoates (PHA), which are biodegradable polymers with industrial applications. The main objective of this study was to evaluate the metabolic capabilities of C. necator for PHA production by integrating different experimental conditions and computational analyses. To achieve this, batch and pulse-fed batch cultures were carried out. For the latter, three different feeding strategies were applied. In the first strategy, two pulses (8.33 mL) of dextrose derived from bitter cassava starch (20 g/L) and ammonium sulfate at a C/N ratio of 73 were added at 24 and 48 h, extending the culture to 120 h. In the second strategy, a single pulse (3.15 mL) of only dextrose (20 g/L) was added at 48 h, with a total cultivation time of 96 h. And in the third strategy, a single pulse (6.14 mL) of only dextrose (20 g/L) was added at 60 h, also extending the culture to 96 h. Batch cultures demonstrated the growth of C. necator, reaching a maximum biomass concentration of 5.17 g/L at 48 h and a polyhydroxybutyrate (PHB) accumulation of 47.1% at the end of the culture (72 h). In the pulse-fed batch cultures, the first strategy extended the exponential growth phase. This led to a gradual accumulation of PHB, reaching a PHB yield of 0.46 g/g and a productivity of 15 mg/(L*h) after 120 h of cultivation. However, the pulse-fed batch cultures, the first strategy resulted in an extended exponential growth phase and gradual PHB accumulation, reaching yields of 0.46 g/g and a productivity of 15.00 mg/(L*h) after 120 hours of cultivation. However, PHB accumulation was 20.57% and 25.12% lower compared to the accumulation observed in the batch culture. In contrast, the third strategy, with a single pulse at 60 h during the stationary phase, resulted in a higher PHB accumulation (52.40%) and productivity (23.22 mg/(L*h)), surpassing the values obtained in batch and the other pulse-feeding strategies. Additionally, the iCNH2025A model represents a refined and highly curated metabolic reconstruction of C. necator, showing significant improvements compared to previous models. With 2,737 reactions, 1,803 unique metabolites, and 1,059 annotated genes, the model integrates key metabolic pathways, including the biosynthesis of PHB and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), as well as central metabolic routes such as the Calvin-Benson-Bassham cycle (CBB), the Entner-Doudoroff (ED) pathway, the Embden-Meyerhof-Parnas (EMP) pathway, and the non-oxidative branch of the pentose phosphate pathway (PPP). The model was validated using MEMOTE, achieving a score of 89% and outperforming previous reconstructions such as RehMBEL1391 and iCN1361. In silico growth simulations with fructose and dextrose showed a high correlation with experimental data (R² = 0.76–0.78), validating the model's predictive capacity. Moreover, it accurately captured the carbon flux toward PHB synthesis under various experimental conditions, consistent with previous studies. Thus, the iCNH2025A model represents a significant advancement in the metabolic modeling of C. necator, offering a highly accurate and validated tool for analyzing its metabolism. Its ability to predict metabolic fluxes and growth rates makes it a valuable resource for industrial biotechnology, supporting future optimization strategies in biopolymer production.