Method of Corynebacterium glutamicum fermentation time extension with high lysine production rate by leucine addition

Noboru Takiguchi, Naoki Fukui, Nobuyuki Shimizu, Hiroshi Shimizu, Suteaki Shioya
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引用次数: 6

Abstract

The effect of leucine addition on the production yield of lysine by Corynebacterium glutamicum AJ-3462 was studied and a method of increasing a fermentation time while maintaining high lysine producing activity was developed. When leucine was not added during the lysine production phase, a high molar production yield of lysine from glucose of 35.6% was obtained. However, lysine production did not continue for a long time and almost stopped at around 90 h. When leucine was added to the medium in the fermentor at 24 h intervals, lysine producing activity was maintained for a long time; however, the production yield of lysine from glucose was reduced to 23.5%. When leucine was added at 30 h intervals, the production yield of lysine from glucose was improved to 32.9%. However, leucine addition did not recover lysine producing activity after 162 h. From these results, in order to extend the fermentation time while maintaining lysine productivity and production yield at high values, a leucine addition strategy was developed as follows. The initial leucine concentration was set as 0.1 g/l. After depletion of leucine, it was added intermittently at 30 h intervals. The interval for intermittent addition was changed to 24 h when a decrease in cellular activity was recognized by on-line monitoring of the lysine production rate based on a metabolic reaction model. As a result, the fermentation time was extended to 174 h, and lysine productivity and total molar production yield of lysine from glucose became 0.104 g/l/h and 29.2%, respectively.

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添加亮氨酸延长谷氨酸棒状杆菌发酵时间高产赖氨酸的方法
研究了添加亮氨酸对谷氨酸棒状杆菌AJ-3462赖氨酸产率的影响,提出了在保持赖氨酸高产活性的同时延长发酵时间的方法。在赖氨酸生产阶段不添加亮氨酸时,葡萄糖赖氨酸的摩尔产率高达35.6%。然而,赖氨酸的产生时间不长,在90 h左右几乎停止。每隔24 h向发酵罐的培养基中添加赖氨酸,赖氨酸的产生活性保持较长时间;然而,葡萄糖的赖氨酸产率降低到23.5%。当每隔30 h添加赖氨酸时,葡萄糖的赖氨酸产率提高到32.9%。然而,添加亮氨酸在162 h后并没有恢复赖氨酸的生产活性。根据这些结果,为了延长发酵时间,同时保持较高的赖氨酸产量和产量,我们制定了亮氨酸添加策略。初始亮氨酸浓度设为0.1 g/l。亮氨酸耗尽后,每隔30 h间歇添加。当基于代谢反应模型在线监测赖氨酸产率发现细胞活性下降时,将间歇添加的间隔改为24 h。结果表明,发酵时间延长至174 h,葡萄糖赖氨酸产率和赖氨酸总摩尔产率分别为0.104 g/l/h和29.2%。
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