Metabolic flux redirection from a central metabolic pathway toward a synthetic pathway using a metabolic toggle switch
Metabolic flux redirection from a central metabolic pathway toward a synthetic pathway using a metabolic toggle switch
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DOI：
10.1016/j.ymben.2014.02.008
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发表时间：
2014-05-01
影响因子：
8.4
通讯作者：
Hanai, Taizo
中科院分区：
文献类型：
--
作者：
Soma, Yuki;Tsuruno, Keigo;Hanai, Taizo
在代谢工程中，通常采用生产途径中基因的过表达和竞争途径中基因的永久敲除来提高生产滴度和产量。然而，删除负责生长和细胞维持的途径以前没有被采用，即使它与生产途径的竞争是明显的。为了优化细菌生长和生产的每个发酵阶段的细胞内代谢，需要采用条件性敲除的方法。我们在大肠杆菌中构建了一个代谢开关作为一种新的条件敲除方法，并将其应用于异丙醇生产。通过关闭gltA中断TCA循环而导致的过量碳通量的重新定向分别将异丙醇生产滴度和产率提高了3.7倍和3.1倍。这种方法是将负责细菌生长和/或细胞维持的碳通量重定向到合成生产途径的有用工具。(C)2014年国际代谢工程学会。爱思唯尔公司出版
Overexpressiun of genes in production pathways and permanent knockout of genes in competing pathways are often employed to improve production titer and yield in metabolic engineering. However, the deletion of a pathway responsible for growth and cell maintenance has not previously been employed, even if its competition with the production pathway is obvious. In order to optimize intracellular metabolism at each fermentation phase for bacterial growth and production, a methodology employing conditional knockout is required. We constructed a metabolic toggle switch in Escherichia coli as a novel conditional knockout approach and applied it to isopropanol production. The resulting redirection of excess carbon flux caused by interruption of the TCA cycle via switching gltA OFF improved isopropanol production titer and yield up to 3.7 and 3.1 times, respectively. This approach is a useful tool to redirect carbon flux responsible for bacterial growth and/or cell maintenance toward a synthetic production pathway. (C) 2014 International Metabolic Engineering Society. Published by Elsevier Inc.