谷氨酸棒杆菌生产异亮氨酸辅因子策略及其基因组整合研究进展  

Cofactor Strategy and Genome Integration of L‑isoleucine Production by Corynebacterium glutamicum

作　　者：靳鑫[1] 王苏蒙 祁庆生[1] 梁泉峰[1] JIN Xin;WANG Sumeng;QI Qingsheng;LIANG Quanfeng(State Key Laboratory of Microbiology,Shandong University,Shandong Qingdao 266237,China)

机构地区：[1]山东大学微生物技术国家重点实验室,山东青岛266237

出　　处：《生物技术进展》2022年第2期176-188,共13页Current Biotechnology

基　　金：国家重点研发计划项目(2021YFC2103600);国家自然科学基金项目(31961133014;31770095;31971336)。

摘　　要：L‑异亮氨酸属于三大支链氨基酸,是人体8种必需氨基酸之一,广泛应用于食品、药品、保健品、化妆品等领域。目前,微生物发酵法是工业生产L‑异亮氨酸的主要方法,其中谷氨酸棒杆菌(Corynebacteriumglutamicum)是发酵生产L‑异亮氨酸的优势菌株,然而随机诱变会使产量的提高能力达到饱和,难以得到更加高产的菌株,因此针对诱变菌株进行理性改造已成为进一步提高产量的主要方式;且随着遗传操作技术在谷氨酸棒杆菌中的应用与优化,代谢工程育种已逐渐取代传统的诱变育种。综述了谷氨酸棒杆菌中L‑异亮氨酸的生物合成途径、代谢调控机制和理性改造L‑异亮氨酸生产菌株的策略,并对辅助因子工程应用于理性改造及对谷氨酸棒杆菌基因组整合策略进行了系统阐述,以期为工业水平稳定生产L‑异亮氨酸高产菌株的基因组整合策略提供参考依据。L‑isoleucine which belongs to three branched chain amino acids,is one of the eight essential amino acids for human body.It is widely used in food,medicine,health products,cosmetics and other fields.At present,microbial fermentation is the main method of industrial production for L‑isoleucine.Corynebacterium glutamicum is the dominant strain for fermentation pro‑duction of L‑isoleucine.However,random mutation saturates the ability to increase yield,so it is difficult to obtain more high‑yield strains.Therefore,rational transformation of mutant strains has become the main way to further improve yield;with the application and optimization of genetic manipulation technology in Corynebacterium glutamicum,metabolic engineering breeding has gradually replaced the traditional mutation breeding.In this paper,the biosynthetic pathway,metabolic regulation mechanism of L‑isoleucine in Corynebacterium glutamicum and the strategy of rational transformation of L‑isoleucine producing strains were reviewed.The application of cofactor engineering in rational transformation and the strategy of genome integration of Corynebacterium glutamicum were systematically described,aiming to provide a reference basis for the genome integration strate‑gy of L‑isoleucine producing strains at the industrial level.

关 键 词：L‑异亮氨酸 生物合成 理性改造 辅助因子工程 基因组整合 

分 类 号：TQ922[轻工技术与工程—发酵工程] Q784[生物学—分子生物学]