BioQuant, Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.
Institute of Biochemical Engineering, University of Stuttgart, Stuttgart, Germany.
J Biotechnol. 2023 Sep 10;374:90-100. doi: 10.1016/j.jbiotec.2023.08.001. Epub 2023 Aug 10.
The fermentation process of milk to yoghurt using Lactobacillus delbrueckii subsp. bulgaricus in co-culture with Streptococcus thermophilus is hallmarked by the breakdown of lactose to organic acids such as lactate. This leads to a substantial decrease in pH - both in the medium, as well as cytosolic. The latter impairs metabolic activities due to the pH-dependence of enzymes, which compromises microbial growth. To quantitatively elucidate the impact of the acidification on metabolism of L. bulgaricus in an integrated way, we have developed a proton-dependent computational model of lactose metabolism and casein degradation based on experimental data. The model accounts for the influence of pH on enzyme activities as well as cellular growth and proliferation of the bacterial population. We used a machine learning approach to quantify the cell volume throughout fermentation. Simulation results show a decrease in metabolic flux with acidification of the cytosol. Additionally, the validated model predicts a similar metabolic behaviour within a wide range of non-limiting substrate concentrations. This computational model provides a deeper understanding of the intricate relationships between metabolic activity and acidification and paves the way for further optimization of yoghurt production under industrial settings.
使用嗜热链球菌与德氏乳杆菌保加利亚亚种共培养发酵牛奶生产酸奶的过程中，乳糖会被分解为乳酸等有机酸。这会导致 pH 值大幅下降——无论是在培养基中还是细胞质中。后者会由于酶对 pH 值的依赖性而损害代谢活动，从而影响微生物的生长。为了全面定量阐明酸化对保加利亚乳杆菌代谢的影响，我们根据实验数据开发了一个基于质子依赖的乳糖代谢和酪蛋白降解的计算模型。该模型考虑了 pH 值对酶活性以及细菌群体的细胞生长和增殖的影响。我们使用机器学习方法来量化整个发酵过程中的细胞体积。模拟结果表明，随着细胞质酸化，代谢通量会下降。此外，经过验证的模型预测在广泛的非限制底物浓度范围内具有相似的代谢行为。该计算模型深入了解了代谢活性和酸化之间的复杂关系，为进一步优化工业条件下的酸奶生产铺平了道路。
