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将酵母发酵的动态通量平衡模型扩展到基因组规模。

Expanding a dynamic flux balance model of yeast fermentation to genome-scale.

作者信息

Vargas Felipe A, Pizarro Francisco, Pérez-Correa J Ricardo, Agosin Eduardo

机构信息

Department of Chemical and Bioprocess Engineering, School of Engineering, Pontificia Universidad Católica de Chile, Casilla, Correo, Santiago CHILE.

出版信息

BMC Syst Biol. 2011 May 19;5:75. doi: 10.1186/1752-0509-5-75.

Abstract

BACKGROUND

Yeast is considered to be a workhorse of the biotechnology industry for the production of many value-added chemicals, alcoholic beverages and biofuels. Optimization of the fermentation is a challenging task that greatly benefits from dynamic models able to accurately describe and predict the fermentation profile and resulting products under different genetic and environmental conditions. In this article, we developed and validated a genome-scale dynamic flux balance model, using experimentally determined kinetic constraints.

RESULTS

Appropriate equations for maintenance, biomass composition, anaerobic metabolism and nutrient uptake are key to improve model performance, especially for predicting glycerol and ethanol synthesis. Prediction profiles of synthesis and consumption of the main metabolites involved in alcoholic fermentation closely agreed with experimental data obtained from numerous lab and industrial fermentations under different environmental conditions. Finally, fermentation simulations of genetically engineered yeasts closely reproduced previously reported experimental results regarding final concentrations of the main fermentation products such as ethanol and glycerol.

CONCLUSION

A useful tool to describe, understand and predict metabolite production in batch yeast cultures was developed. The resulting model, if used wisely, could help to search for new metabolic engineering strategies to manage ethanol content in batch fermentations.

摘要

背景

酵母被认为是生物技术产业中用于生产多种增值化学品、酒精饮料和生物燃料的主力军。发酵过程的优化是一项具有挑战性的任务,而能够准确描述和预测不同遗传和环境条件下发酵过程及产物的动态模型对此有很大帮助。在本文中,我们利用实验确定的动力学约束条件,开发并验证了一个基因组规模的动态通量平衡模型。

结果

合适的维持、生物质组成、无氧代谢和营养物质摄取方程是提高模型性能的关键,特别是对于预测甘油和乙醇的合成。酒精发酵中主要代谢产物的合成和消耗预测曲线与在不同环境条件下从众多实验室和工业发酵中获得的实验数据密切吻合。最后,基因工程酵母的发酵模拟结果与先前报道的关于乙醇和甘油等主要发酵产物最终浓度的实验结果非常相似。

结论

开发了一个用于描述、理解和预测分批酵母培养中代谢产物生成的有用工具。如果明智地使用,所得模型有助于寻找新的代谢工程策略来控制分批发酵中的乙醇含量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69e9/3118138/f8e44819d780/1752-0509-5-75-1.jpg

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