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首页> 外文期刊>Scientific reports. >Genome-scale modeling and transcriptome analysis of Leuconostoc mesenteroides unravel the redox governed metabolic states in obligate heterofermentative lactic acid bacteria
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Genome-scale modeling and transcriptome analysis of Leuconostoc mesenteroides unravel the redox governed metabolic states in obligate heterofermentative lactic acid bacteria

机译:Leuconostoc Mesenteroides揭开氧化还原的基因组规模造型及转录组分析redox治理代谢态in incrige异质乳酸细菌

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摘要

Obligate heterofermentative lactic acid bacteria (LAB) are well-known for their beneficial health effects in humans. To delineate the incompletely characterized metabolism that currently limits their exploitation, at systems-level, we developed a genome-scale metabolic model of the representative obligate heterofermenting LAB, Leuconostoc mesenteroides (iLME620). Constraint-based flux analysis was then used to simulate several qualitative and quantitative phenotypes of L. mesenteroides, thereby evaluating the model validity. With established predictive capabilities, we subsequently employed iLME620 to elucidate unique metabolic characteristics of L. mesenteroides, such as the limited ability to utilize amino acids as energy source, and to substantiate the role of malolactic fermentation (MLF) in the reduction of pH-homeostatic burden on F0F1-ATPase. We also reported new hypothesis on the MLF mechanism that could be explained via a substrate channelling-like phenomenon mainly influenced by intracellular redox state rather than the intermediary reactions. Model simulations further revealed possible proton-symporter dependent activity of the energy efficient glucose-phosphotransferase system in obligate heterofermentative LAB. Moreover, integrated transcriptomic analysis allowed us to hypothesize transcriptional regulatory bias affecting the intracellular redox state. The insights gained here about the low ATP-yielding metabolism of L. mesenteroides, dominantly controlled by the cellular redox state, could potentially aid strain design for probiotic and cell factory applications.
机译:众所周知,对人类的有益健康效应是众所周知的,致异质乳酸菌(实验室)。为了描绘目前限制其剥削的未完全表征的新陈代谢,在系统级别,我们开发了代表性的基因组级代谢模型,Iuconostoc肠系膜(ILME620)。然后使用基于约束的助焊剂分析来模拟L. Mesenteroides的几种定性和定量表型,从而评估模型有效性。具有既定的预测能力,我们随后使用ILME620来阐明L. Mesenteroides的独特代谢特征,例如利用氨基酸作为能量来源的有限能力,并证实了恶性发酵(MLF)在降低pH-稳态的减少中的作用F0F1-ATPase的负担。我们还报道了在MLF机制上的新假设,其可以通过基材沟道样现象来解释,所述现象主要受细胞内氧化还原状态而不是中间反应的影响。模型模拟进一步揭示了在普通的异质型实验室中的节能葡萄糖 - 磷酸转移酶系统的质量依赖性活性。此外,集成的转录组分析使我们能够假设影响细胞内氧化还原状态的转录调节偏压。这里获得的关于L. Mesenteroides的低ATP产量代谢的见解,由细胞氧化还原状态占主导地位,可能潜在地帮助益生菌和细胞厂应用的菌株设计。

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