Manually curated genome-scale reconstruction of the metabolic network of Bacillus megaterium DSM319
Manually curated genome-scale reconstruction of the metabolic network of Bacillus megaterium DSM319
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DOI：
10.1038/s41598-019-55041-w
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发表时间：
2019-12-10
影响因子：
4.6
通讯作者：
Marashi, Sayed-Amir
中科院分区：
文献类型：
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作者：
Aminian-Dehkordi, Javad;Mousavi, Seyyed Mohammad;Marashi, Sayed-Amir
巨大芽孢杆菌是一种广泛用于生产酶和重组蛋白的工业生物技术以及生物浸提工艺的微生物。精确了解其代谢对于设计工程策略以进一步优化B是必不可少的。用于生物技术应用。在这里，我们提出了一个基因组规模的代谢模型的B。megaterium DSM 319，iJA 1121，这是代谢网络协调过程的结果。该模型包括1709个反应，1349个代谢产物和1121个基因。基于多基因组比对和其他芽孢杆菌属物种的可用基因组规模代谢模型，我们使用自动化方法构建了一个草图网络，然后进行手动管理。使用间隙填充过程进行改进。基于约束的建模被用来仔细检查网络功能。进行表型分析以验证使用不同底物的模型的生长行为。为了验证模型的准确性，在文献中报道的实验数据（生长行为模式，代谢产物的生产能力，代谢通量分析使用C-13葡萄糖和甲醛抑制作用）面临的模型预测。这表明计算机模拟结果与实验数据之间非常一致。例如，我们对B中脂肪酸生物合成和脂质积累的计算机模拟研究。megaterium强调了为发酵目的采用适当碳源的重要性。我们的结论是，基因组规模的代谢模型iJA 1121代表了一个有用的工具，系统分析，并进一步加深了我们的理解的代谢B。巨大的
Bacillus megaterium is a microorganism widely used in industrial biotechnology for production of enzymes and recombinant proteins, as well as in bioleaching processes. Precise understanding of its metabolism is essential for designing engineering strategies to further optimize B. megaterium for biotechnology applications. Here, we present a genome-scale metabolic model for B. megaterium DSM319, iJA1121, which is a result of a metabolic network reconciliation process. The model includes 1709 reactions, 1349 metabolites, and 1121 genes. Based on multiple-genome alignments and available genome-scale metabolic models for other Bacillus species, we constructed a draft network using an automated approach followed by manual curation. The refinements were performed using a gap-filling process. Constraint-based modeling was used to scrutinize network features. Phenotyping assays were performed in order to validate the growth behavior of the model using different substrates. To verify the model accuracy, experimental data reported in the literature (growth behavior patterns, metabolite production capabilities, metabolic flux analysis using C-13 glucose and formaldehyde inhibitory effect) were confronted with model predictions. This indicated a very good agreement between in silico results and experimental data. For example, our in silico study of fatty acid biosynthesis and lipid accumulation in B. megaterium highlighted the importance of adopting appropriate carbon sources for fermentation purposes. We conclude that the genome-scale metabolic model iJA1121 represents a useful tool for systems analysis and furthers our understanding of the metabolism of B. megaterium.