A curated genome-scale metabolic model of Bordetella pertussis metabolism.
A curated genome-scale metabolic model of Bordetella pertussis metabolism.
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DOI：
10.1371/journal.pcbi.1005639
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发表时间：
2017-07
影响因子：
4.3
通讯作者：
Colijn C
中科院分区：
文献类型：
--
作者：
Fyson N;King J;Belcher T;Preston A;Colijn C
革兰氏阴性菌百日咳杆菌是百日咳的病原体，百日咳是一种严重的呼吸道感染，每年在全世界造成数十万人死亡。有有效的疫苗，但它们的生产需要大量的B。百日咳。很不幸，B。百日咳菌在培养物中生长相对缓慢，生物量产量低，生长特征多变。B。百日咳还需要相对昂贵的生长培养基。我们提出了一个新的，策划通量平衡分析为基础的模型B。百日咳代谢我们用实验确定的生物量目标函数增强了模型，并进行了大量的手动管理。我们使用转座子定向插入测序（TraDIS）方法对必需基因进行全基因组筛选来测试模型的预测。我们测试了它对培养基中不同碳源生长的预测。该模型以83%的准确度预测了必要性，并正确预测了谷氨酸盐：富马酸盐比例增加时生长的改善。我们以SBML格式提供模型，沿着基因重要性预测。代谢通量模型已被用来了解生物体如何适应不同的生长条件下，他们的代谢，并发现越来越多的应用在合成生物学和生物技术。在这一领域取得进展的一个障碍是新生物体代谢通量模型的构建和管理。在这里，我们提出了一个策划的基因组规模的代谢流模型百日咳博德特氏菌，百日咳的病原体。生产百日咳疫苗需要生长B。大量的百日咳。然而，它的生长相对缓慢，生物量的最终产量相对较低，生长特性可能是可变的。理解B。百日咳代谢可应用于改进疫苗生产，以及了解这种生物体的基本生物学。
The Gram-negative bacterium Bordetella pertussis is the causative agent of whooping cough, a serious respiratory infection causing hundreds of thousands of deaths annually worldwide. There are effective vaccines, but their production requires growing large quantities of B. pertussis. Unfortunately, B. pertussis has relatively slow growth in culture, with low biomass yields and variable growth characteristics. B. pertussis also requires a relatively expensive growth medium. We present a new, curated flux balance analysis-based model of B. pertussis metabolism. We enhance the model with an experimentally-determined biomass objective function, and we perform extensive manual curation. We test the model’s predictions with a genome-wide screen for essential genes using a transposon-directed insertional sequencing (TraDIS) approach. We test its predictions of growth for different carbon sources in the medium. The model predicts essentiality with an accuracy of 83% and correctly predicts improvements in growth under increased glutamate:fumarate ratios. We provide the model in SBML format, along with gene essentiality predictions. Metabolic flux models have been used to understand how organisms adapt their metabolism under different growth conditions, and are finding increasing application in synthetic biology and biotechnology. One barrier to progress in this field is the construction and curation of metabolic flux models for new organisms. Here we present a curated genome-scale metabolic flux model for Bordetella pertussis, the causative agent of whooping cough. Producing vaccines against whooping cough requires growing B. pertussis in large volumes. However, its growth is relatively slow, final yields of biomass are relatively low and growth characteristics can be variable. Understanding B. pertussis metabolism has applications to improving vaccine production, as well as in understanding the basic biology of this organism.
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影响因子：
4.4
作者：
Alam MT;Merlo ME;STREAM Consortium;Hodgson DA;Wellington EM;Takano E;Breitling R
通讯作者：
Breitling R
影响因子：
3.7
作者：
Saulnier DM;Santos F;Roos S;Mistretta TA;Spinler JK;Molenaar D;Teusink B;Versalovic J
通讯作者：
Versalovic J
影响因子：
7
作者：
Langridge, Gemma C.;Phan, Minh-Duy;Turner, A. Keith
通讯作者：
Turner, A. Keith
DOI：
10.3181/00379727-45-11763
发表时间：
1940-10-01
影响因子：
--
作者：
Hornibrook, JW
通讯作者：
Hornibrook, JW
影响因子：
--
作者：
Kim J;Reed JL
通讯作者：
Reed JL