Mechanistic insights into bacterial metabolic reprogramming from omics-integrated genome-scale models
Mechanistic insights into bacterial metabolic reprogramming from omics-integrated genome-scale models
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DOI：
10.1038/s41540-019-0121-4
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发表时间：
2020-01-07
影响因子：
4
通讯作者：
van der Meer, Jan R.
中科院分区：
文献类型：
--
作者：
Hadadi, Noushin;Pandey, Vikash;van der Meer, Jan R.
了解单个细菌菌株的适应性反应对于微生物组工程方法来说是至关重要的，这些微生物组工程方法为复杂的微生物组引入新的功能，例如用于土壤生物修复的异生化合物代谢。适应需要细胞的新陈代谢重新编程，这可以被多组学捕获，但这些数据仍然具有强大的挑战性，难以解释和预测。在这里，我们提出了一种新的方法，将基因组规模的代谢建模与转录组学和外代谢组学相结合，这两种方法都是研究动态种群行为的常用工具。作为一个现实的演示，我们开发了一种加速土壤微生物体内单芳烃代谢的候选生物增强剂--韦氏假单胞菌1YdBTEX2的基因组规模模型，同时收集了韦氏假单胞菌在生长阶段转变过程中代谢的实验数据。从综合模型中预测的韦氏肺孢子虫的生长速度和特定的代谢过程与实验观察结果非常吻合。我们的结论是，综合和基于网络的分析可以帮助建立准确捕捉细菌适应反应的预测模型。进一步开发和测试这样的模型可能会极大地提高在更复杂的系统中成功建立细菌接种剂的能力。
Understanding the adaptive responses of individual bacterial strains is crucial for microbiome engineering approaches that introduce new functionalities into complex microbiomes, such as xenobiotic compound metabolism for soil bioremediation. Adaptation requires metabolic reprogramming of the cell, which can be captured by multi-omics, but this data remains formidably challenging to interpret and predict. Here we present a new approach that combines genome-scale metabolic modeling with transcriptomics and exometabolomics, both of which are common tools for studying dynamic population behavior. As a realistic demonstration, we developed a genome-scale model of Pseudomonas veronii 1YdBTEX2, a candidate bioaugmentation agent for accelerated metabolism of mono-aromatic compounds in soil microbiomes, while simultaneously collecting experimental data of P. veronii metabolism during growth phase transitions. Predictions of the P. veronii growth rates and specific metabolic processes from the integrated model closely matched experimental observations. We conclude that integrative and network-based analysis can help build predictive models that accurately capture bacterial adaptation responses. Further development and testing of such models may considerably improve the successful establishment of bacterial inoculants in more complex systems.