In silico screening of triple reaction knockout Escherichia coli strains for overproduction of useful metabolites
In silico screening of triple reaction knockout Escherichia coli strains for overproduction of useful metabolites
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DOI：
10.1016/j.jbiosc.2012.09.004
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发表时间：
2013-02-01
影响因子：
2.8
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
--
作者：
Ohno, Satoshi;Furusawa, Chikara;Shimizu, Hiroshi
为了有效地利用微生物生产工业上有用的代谢物，设计适合生产的代谢网络是很重要的。为此，基于约束的代谢通量模拟是预测反应敲除对目标生产率影响的有力工具。在这项研究中，使用基于约束的代谢模拟，在电子筛选中筛选出能够提高工程大肠杆菌生产1-丁醇、1-丙醇和1，3-丙二醇的基因敲除候选集。使用简化的代谢模型来评估由所有可能的三重反应敲除集合引起的代谢变化，该模型的构建是为了显著降低计算成本。结果证明了通过基因破坏来提高目标生产力的策略，其中一些策略是以前的筛选方法无法实现的。这样的淘汰战略可以支持目标生产率的进一步提高。(C)2012年，日本生物技术学会。版权所有。
For efficient production of industrially useful metabolites by microorganisms, it is important to design metabolic networks suitable for production. For this purpose, constraint-based metabolic flux simulation is a powerful tool to predict the effect of reaction knockouts on target productivity. In this study, using constraint-based metabolic simulation, in silico screening was performed to identify knockout candidate sets that increase the productivity of 1-butanol, 1-propanol, and 1,3-propanediol by engineered Escherichia coli. Metabolic changes caused by all possible sets of triple reaction knockouts were evaluated using a reduced metabolic model, which was constructed to significantly reduce the computational cost. The results demonstrated the strategies to improve target productivity by gene disruption; some of them could not be achieved by previous screening methods. Such knockout strategies can support further improvements of the target productivity. (C) 2012, The Society for Biotechnology, Japan. All rights reserved.