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用于尸胺生产的[代谢工程]

[Metabolic engineering of for the production of cadaverine].

作者信息

Liu Cunping, Gao Cong, Li Xiaomin, Chen Xiulai, Wu Jing, Song Wei, Wei Wanqing, Liu Liming

机构信息

School of Biotechnology, Jiangnan University, Wuxi 214122, Jiangsu, China.

School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, Jiangsu, China.

出版信息

Sheng Wu Gong Cheng Xue Bao. 2024 Aug 25;40(8):2403-2417. doi: 10.13345/j.cjb.240144.

Abstract

Cadaverine is a fundamental C5 building block in the production of polyamides. Due to the limited regeneration efficiency of intracellular pyridoxal 5'-phosphate (PLP), the current fermentation-based production of cadaverine exhibits low efficiency. In this study, we developed an strain L01 by introducing lysine decarboxylase (lysine decarboxylase, LDC, a key enzyme in the synthesis of cadaverine) into a lysine-producing strain . LY-4, achieving a cadaverine tier of 1.07 g/L in shake flask fermentation. Subsequently, a dual metabolic pathway enhancement strategy was proposed to synergistically strengthen both endogenous and exogenous PLP synthesis modules, thereby improving intracellular PLP synthesis. The optimized strain L11 achieved a cadaverine titer of 9.23 g/L in shake flask fermentation. Finally, the fermentation process for cadaverine production by strain L11 was optimized in a 5 L fermenter. After 48 h of fed-batch fermentation, the engineered strain L11 achieved the cadaverine titer, yield, and productivity of 54.43 g/L, 0.22 g/g, and 1.13 g/(L·h), respectively. This study provides a theoretical and technical foundation for establishing microbial cell factories for bioamine production.

摘要

尸胺是聚酰胺生产中的一种基本的C5构建模块。由于细胞内磷酸吡哆醛(PLP)的再生效率有限,目前基于发酵的尸胺生产效率较低。在本研究中,我们通过将赖氨酸脱羧酶(尸胺合成中的关键酶,赖氨酸脱羧酶,LDC)引入产赖氨酸菌株LY - 4中,构建了菌株L01,在摇瓶发酵中实现了1.07 g/L的尸胺产量。随后,提出了一种双代谢途径增强策略,以协同增强内源性和外源性PLP合成模块,从而提高细胞内PLP的合成。优化后的菌株L11在摇瓶发酵中实现了9.23 g/L的尸胺效价。最后,在5 L发酵罐中对菌株L11生产尸胺的发酵过程进行了优化。经过48 h的补料分批发酵,工程菌株L11的尸胺效价、产量和生产率分别达到了54.43 g/L、0.22 g/g和1.13 g/(L·h)。本研究为建立用于生物胺生产的微生物细胞工厂提供了理论和技术基础。

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