From zero to hero-Design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine production
From zero to hero-Design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine production
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DOI：
10.1016/j.ymben.2011.01.003
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发表时间：
2011-03-01
影响因子：
8.4
通讯作者：
Wittmann, Christoph
中科院分区：
文献类型：
--
作者：
Becker, Judith;Zelder, Oskar;Wittmann, Christoph
在这里，我们描述了一个遗传定义的L-赖氨酸高产谷氨酸棒杆菌菌株的野生型系统代谢工程的发展。实施只有12个定义的基因组为基础的变化，编码中心代谢酶的基因重定向主要的碳通量，如所需的最佳途径的使用预测的计算机模拟。最后将C.谷氨酸菌的赖氨酸产量为0.55 g/g葡萄糖，赖氨酸效价为120 g L ~（-1），分批补料发酵生产能力为4.0 g L ~（-1）h ~（-1）。在工程化过程中，野生型的特定葡萄糖摄取速率可以完全保持，提供了高度可行的生产者。对于这些关键标准，本研究中创建的遗传定义菌株处于过去50年中开发的经典衍生生产者的最大限度。这是第一次报告的合理衍生的赖氨酸生产菌株，可能与工业应用的竞争。基于设计的代谢工程策略可以作为合理开发微生物作为生物生产的高效细胞工厂的一般概念。(C)2011 Elsevier Inc. All rights reserved.
Here, we describe the development of a genetically defined strain of L-lysine hyperproducing Corynebacterium glutamicum by systems metabolic engineering of the wild type. Implementation of only 12 defined genome-based changes in genes encoding central metabolic enzymes redirected major carbon fluxes as desired towards the optimal pathway usage predicted by in silico modeling. The final engineered C. glutamicum strain was able to produce lysine with a high yield of 0.55 g per gram of glucose, a titer of 120 g L-1 lysine and a productivity of 4.0 g L-1 h(-1) in fed-batch culture. The specific glucose uptake rate of the wild type could be completely maintained during the engineering process, providing a highly viable producer. For these key criteria, the genetically defined strain created in this study lies at the maximum limit of classically derived producers developed over the last fifty years. This is the first report of a rationally derived lysine production strain that may be competitive with industrial applications. The design-based strategy for metabolic engineering reported here could serve as general concept for the rational development of microorganisms as efficient cellular factories for bio-production. (C) 2011 Elsevier Inc. All rights reserved.