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多变量模块化代谢工程用于ESCHERICHIA大肠杆菌中增强的L-氨酸生物合成

Zhongcai Li^1,2, Qian Liu^1,3, Jiahui Sun^1,4

¹State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.

Biotechnology for biofuels and bioproducts

|June 13, 2023

概括

研究人员对大肠杆菌进行了高水平L-氨酸生产的工程,实现了创纪录的21.28g/L标位. 这一突破克服了工业应用微生物L-氨酸合成方面的挑战.

科学领域:

代谢工程是代谢工程.
合成生物学合成生物学
工业生物技术工业生物技术

背景情况:

甲氨酸是唯一不通过工业发酵生产的散装氨基酸.
由于复杂的生物合成,开发用于高水平L-氨酸生产的微生物菌株具有挑战性.
目前的生产方法有限,需要新的发酵方法.

研究的目的:

设计一种微生物菌株,以便在工业规模高效地生产L-氨酸.
为了克服L-氨酸生物合成途径中的代谢瓶.
建立一个发酵平台,以实现成本效益高的L-氨酸制造.

主要方法:

埃舍里奇亚大肠杆菌的合理代谢工程 W3110.0.
在L-同类素O-基转移酶 (MetA) 的位点定向突变和基因过度表达 (metA^fbr,metC,yjeH).
基因删除 (pykA,pykF) 和加强L-氨酸合成模块 (cysE,serA,cysDN).
优化发酵条件,包括添加氨硫酸硫酸盐.

主要成果:

最初的工程增加了L-methionine到2.51g/L的震动瓶.
加强L-氨酸的供应增加了52.9%的L-氨酸生产,并减少了29.1%的L-氨酸副产品.
最后的工程菌株 (MET17) 在64小时内在5L发酵器中达到21.28g/L的纪录标位.

结论:

通过合理的代谢工程,成功开发出一种高效的L-甲氨酸生产菌株.
工程化大肠杆菌为工业L-氨酸生产提供了一个强大的平台.
这项研究向可持续和高效的L-氨酸制造业取得了重大进展.

关键词:

囊氨酸的 γ-合成酶.埃舍里希亚大肠杆菌 (Escherichia coli) 是一个大肠杆菌.对于L-Methionine来说,这是一个非常好的方法.代谢工程是代谢工程.多变量模块化多变量

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