文献类型：期刊文献

英文题名：Engineering Escherichia coli for l-Threonine Hyperproduction Based on Multidimensional Optimization Strategies

作者：Zhao, Zhenqiang[1,2];You, Jiajia[1,2];Shi, Xuanping[1,2];Zhu, Rongshuai[1,2];Yang, Fengyu[1,2];Xu, Meijuan[1,2];Shao, Minglong[1,2];Zhang, Rongzhen[1];Zhao, Youxi[3];Rao, Zhiming[1,2]

第一作者：Zhao, Zhenqiang

通讯作者：Rao, ZM[1];Rao, ZM[2];Zhao, YX[3]

机构：[1]Jiangnan Univ, Sch Biotechnol, Key Lab Ind Biotechnol, Minist Educ, Wuxi 214122, Jiangsu, Peoples R China;[2]JITRI, Inst Future Food & Technol, Yixing 214200, Peoples R China;[3]Beijing Union Univ, Coll Biochem Engn, Beijing 100023, Peoples R China

第一机构：Jiangnan Univ, Sch Biotechnol, Key Lab Ind Biotechnol, Minist Educ, Wuxi 214122, Jiangsu, Peoples R China

通讯机构：[1]corresponding author), Jiangnan Univ, Sch Biotechnol, Key Lab Ind Biotechnol, Minist Educ, Wuxi 214122, Jiangsu, Peoples R China;[2]corresponding author), JITRI, Inst Future Food & Technol, Yixing 214200, Peoples R China;[3]corresponding author), Beijing Union Univ, Coll Biochem Engn, Beijing 100023, Peoples R China.|[1141726]北京联合大学生物化学工程学院;[11417]北京联合大学;

年份：2024

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001327127000001)】；

基金：The authors thank the National Key Research and Development Program of China (2021YFC2100900), The National Natural Science Foundation of China (32071470), the National First-class Discipline Program of Light Industry Technology and Engineering (QGJC20230201), the Open Funding Project of Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University (KLIB-KF202102), the Program of Introducing Talents of Discipline to Universities (111-2-06), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX22-2369) for their support.

语种：英文

外文关键词：multidimensional engineering; L-threonine; tolerance; transcriptional regulator; glucose utilization

摘要：Exploring effective remodeling strategies to further improve the productivity of high-yield strains is the goal of biomanufacturing. However, the lack of insight into host-specific metabolic networks prevents timely identification of useful engineering targets. Here, multidimensional engineering strategies were implemented to optimize the global metabolic network for improving l-threonine production. First, the metabolic bottleneck for l-threonine synthesis was eliminated by synergistic utilization of NADH and an enhanced ATP supply. Carbon fluxes were redistributed into the TCA cycle by rationally regulating the GltA activity. Subsequently, the stress global response regulator UspA was identified to enhance l-threonine production by a transcriptomic analysis. Then, l-threonine productivity was improved by enhancing the host's stress resistance and releasing the inhibitory reaction of glucose utilization. Eventually, the l-threonine yield of THRH16 reached 170.3 g/L and 3.78 g/L/h in a 5 L bioreactor, which is the highest production index reported. This study provides rational guidance for increasing the productivity of other chemicals.