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重建和分析马克斯克鲁维酵母基因组规模代谢模型。

Reconstruction and analysis of a Kluyveromyces marxianus genome-scale metabolic model.

机构信息

Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE412 96, Gothenburg, Sweden.

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK2800, Lyngby, Denmark.

出版信息

BMC Bioinformatics. 2019 Nov 6;20(1):551. doi: 10.1186/s12859-019-3134-5.

Abstract

BACKGROUND

Kluyveromyces marxianus is a thermotolerant yeast with multiple biotechnological potentials for industrial applications, which can metabolize a broad range of carbon sources, including less conventional sugars like lactose, xylose, arabinose and inulin. These phenotypic traits are sustained even up to 45 °C, what makes it a relevant candidate for industrial biotechnology applications, such as ethanol production. It is therefore of much interest to get more insight into the metabolism of this yeast. Recent studies suggested, that thermotolerance is achieved by reducing the number of growth-determining proteins or suppressing oxidative phosphorylation. Here we aimed to find related factors contributing to the thermotolerance of K. marxianus.

RESULTS

Here, we reported the first genome-scale metabolic model of Kluyveromyces marxianus, iSM996, using a publicly available Kluyveromyces lactis model as template. The model was manually curated and refined to include the missing species-specific metabolic capabilities. The iSM996 model includes 1913 reactions, associated with 996 genes and 1531 metabolites. It performed well to predict the carbon source utilization and growth rates under different growth conditions. Moreover, the model was coupled with transcriptomics data and used to perform simulations at various growth temperatures.

CONCLUSIONS

K. marxianus iSM996 represents a well-annotated metabolic model of thermotolerant yeast, which provides a new insight into theoretical metabolic profiles at different temperatures of K. marxianus. This could accelerate the integrative analysis of multi-omics data, leading to model-driven strain design and improvement.

摘要

背景

马克斯克鲁维酵母是一种耐热酵母,具有多种生物技术潜力,可用于工业应用,能够代谢广泛的碳源,包括乳糖、木糖、阿拉伯糖和菊粉等不太常规的糖。这些表型特征甚至在 45°C 时仍然得以维持,这使得它成为工业生物技术应用(如乙醇生产)的一个相关候选者。因此,深入了解这种酵母的代谢情况非常重要。最近的研究表明,耐热性是通过减少决定生长的蛋白质数量或抑制氧化磷酸化来实现的。在这里,我们旨在寻找与马克斯克鲁维酵母耐热性相关的因素。

结果

在这里,我们报告了第一个马克斯克鲁维酵母的基因组规模代谢模型 iSM996,该模型使用了公开的乳酸克鲁维酵母模型作为模板。该模型经过手动注释和优化,以包含缺失的物种特异性代谢能力。iSM996 模型包含 1913 个反应,与 996 个基因和 1531 个代谢物相关。它能够很好地预测不同生长条件下的碳源利用和生长速率。此外,该模型与转录组学数据耦合,并用于在不同生长温度下进行模拟。

结论

iSM996 代表了一种耐热酵母的良好注释代谢模型,为马克斯克鲁维酵母在不同温度下的理论代谢谱提供了新的见解。这可以加速多组学数据的综合分析,从而导致基于模型的菌株设计和改进。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7129/6833147/4a0ac86b2f4b/12859_2019_3134_Fig1_HTML.jpg

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