دانلود رایگان مقاله مدلسازی سینتیک بچ تولید کاروتنوئید هوازی

Abstract

Carotenes such as β-carotene have a positive impact in human health as a precursor of vitamin A. The structural complexity of these compounds makes chemical synthesis a difficult option, facilitating the need for their biological production. Reliable mathematical models for batch cultivation are developed to describe the glucose consumption, product formation and depletion, and β-carotene production of the Saccharomyces cerevisiae strain mutant SM14 with 20 g/L glucose as the carbon source. Parameter estimation for the models employ an objective function minimizing an expression that uses the coefficient of determination R2, which avoids the necessity of weighting or normalizing the equations. Comparison with experimental data shows that the developed models show a satisfactory prediction of the overflow metabolism that is happening in the cell. Additionally, local and global sensitivity analysis of the models with respect to the optimal parameters is also studied and further show that the models developed here accurately describe trends in the dynamic states of the bioreactor during batch fermentation.

4. Conclusions

This study develops models and estimates the parameters necessary for accuratelydescribing the growthof S. cerevisiae SM14 and the resulting product profiles, specifically glucose, ethanol, acetic acid, and -carotene. Results indicate that the proposed model and estimated parameters are sufficient for describing the growth with glucose consumption and subproducts formation and depletion in batch cultures of S. cerevisiae SM14. Additionally, utilization of the coefficient of determination R2 in the objective function provides a reliable optimal solution for parameter estimation of the model equations. It avoids the normalization of the equations or the weighting of them. The local sensitivity analysis reflects the inhibition effect of the ethanol and acetic acid concentration in the system and also indicates for which parameters we must have accurate parameter estimation in order to develop a suitable description of the cultivation process. Global sensitivity analysis gives an understanding of the mathematical models in all the input space. The results show appropriate connections between the model variance, parameters of study, and characteristics of the cultivation process. The methods presented here have a much wider application than the single case study of -carotene production from genetically altered S. cerevisiae. Modified versions of these models and methods can be applied to any biological system for which there is a set of sub-products that experience generation and depletion through the course of a single batch fermentation. Additionally, the models described for this specific case study can be used in future optimization and controls studies, including applications in fedbatch and continuous production processes. Finally, knowledge of the S. cerevisiae kinetics is the first step toward the analysis largescale production for which the economic impact of biologically produced nutraceuticals can be ascertained.