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在氮饥饿条件下利用解脂耶氏酵母从葡萄糖中模拟和优化脂类积累。

Modeling and optimization of lipid accumulation by Yarrowia lipolytica from glucose under nitrogen depletion conditions.

机构信息

LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, France.

LAAS-CNRS, Université de Toulouse, CNRS, UPS, Toulouse, France.

出版信息

Biotechnol Bioeng. 2018 May;115(5):1137-1151. doi: 10.1002/bit.26537. Epub 2018 Jan 31.

DOI:10.1002/bit.26537
PMID:29288574
Abstract

Oleaginous yeasts have been seen as a feasible alternative to produce the precursors of biodiesel due to their capacity to accumulate lipids as triacylglycerol having profiles with high content of unsaturated fatty acids. The yeast Yarrowia lipolytica is a promising microorganism that can produce lipids under nitrogen depletion conditions and excess of the carbon source. However, under these conditions, this yeast also produces citric acid (overflow metabolism) decreasing lipid productivity. This work presents two mathematical models for lipid production by Y. lipolytica from glucose. The first model is based on Monod and inhibition kinetics, and the second one is based on the Droop quota model approach, which is extended to yeast. The two models showed good agreements with the experimental data used for calibration and validation. The quota based model presented a better description of the dynamics of nitrogen and glucose dynamics leading to a good management of N/C ratio which makes this model interesting for control purposes. Then, quota model was used to evaluate, by means of simulation, a scenario for optimizing lipid productivity and lipid content. For that, a control strategy was designed by approximating the flow rates of glucose and nitrogen with piecewise linear functions. Simulation results achieved productivity of 0.95 g L  hr and lipid content fraction of 0.23 g g , which indicates that this strategy is a promising alternative for the optimization of lipid production.

摘要

产油酵母因其能够积累富含不饱和脂肪酸的三酰基甘油形式的脂类,被视为生产生物柴油前体的可行替代品。解脂耶氏酵母是一种很有前途的微生物,能够在氮源耗尽和碳源过剩的条件下生产脂质。然而,在这些条件下,这种酵母也会产生柠檬酸(代谢物溢生),从而降低脂质生产力。本文提出了两种基于葡萄糖的产油酵母产油的数学模型。第一个模型基于 Monod 和抑制动力学,第二个模型基于 Droop 定额模型方法,并将其扩展到酵母中。两个模型均与用于校准和验证的实验数据具有良好的一致性。基于定额的模型对氮和葡萄糖动力学的动态进行了更好的描述,从而实现了 N/C 比的良好管理,这使得该模型在控制方面具有吸引力。然后,通过模拟,利用定额模型评估了优化产油率和产油率的方案。为此,通过用分段线性函数近似葡萄糖和氮的流速,设计了一种控制策略。模拟结果达到了 0.95 g/L·hr 的生产力和 0.23 g/g 的脂质含量分数,这表明该策略是优化脂质生产的一种有前途的替代方法。

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