Genomically and biochemically accurate metabolic reconstruction of Methanosarcina barkeri Fusaro, iMG746
Genomically and biochemically accurate metabolic reconstruction of Methanosarcina barkeri Fusaro, iMG746
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DOI：
10.1002/biot.201200266
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发表时间：
2013-09-01
影响因子：
4.7
通讯作者：
Price, Nathan D.
中科院分区：
文献类型：
--
作者：
Gonnerman, Matthew C.;Benedict, Matthew N.;Price, Nathan D.
巴氏甲烷单胞菌是一种以厌氧方式产生甲烷的古生菌，甲烷是其新陈代谢的主要副产品。巴氏支原体可以利用几种底物来生产三磷酸腺苷和生物质，包括甲醇、乙酸盐、甲胺以及氢和二氧化碳的组合。2006年，巴氏分支杆菌iAF692的代谢重建是基于一份草稿基因组注释产生的。IAF692的重建使首次对古生代进行基因组规模的模拟成为可能。自从巴克分枝杆菌的第一次代谢重建发表以来，更多的基因组、生化和表型数据阐明了几条代谢途径。我们已经使用了这些新获得的数据来改进Barkeri的代谢重建。使用更新的模型iMG746进行的建模模拟提高了预测基因敲除表型和模拟批量生长行为的准确性。我们使用该模型检验了基因敲除致死率数据，并对不同生长条件下的代谢调节进行了预测。因此，巴氏分支杆菌代谢的最新代谢重建是预测细胞行为、研究产甲烷生活方式、指导实验研究以及做出与代谢工程应用相关的预测的有用工具。
Methanosarcina barkeri is an Archaeon that produces methane anaerobically as the primary byproduct of its metabolism. M. barkeri can utilize several substrates for ATP and biomass production including methanol, acetate, methyl amines, and a combination of hydrogen and carbon dioxide. In 2006, a metabolic reconstruction of M. barkeri, iAF692, was generated based on a draft genome annotation. The iAF692 reconstruction enabled the first genome-Scale simulations for Archaea. Since the publication of the first metabolic reconstruction of M. barkeri, additional genomic, biochemical, and phenotypic data have clarified several metabolic pathways. We have used this newly available data to improve the M. barkeri metabolic reconstruction. Modeling simulations using the updated model, iMG746, have led to increased accuracy in predicting gene knockout phenotypes and simulations of batch growth behavior. We used the model to examine knockout lethality data and make predictions about metabolic regulation under different growth conditions. Thus, the updated metabolic reconstruction of M. barkeri metabolism is a useful tool for predicting cellular behavior, studying the methanogenic lifestyle, guiding experimental studies, and making predictions relevant to metabolic engineering applications.