文献类型： 外文期刊

作者： Wang, Shiyi ¹ ; Zhu, Jiang ¹ ; Zhao, Yiwen ¹ ; Mao, Shufen ¹ ; He, Yihui ¹ ; Wang, Feixiang ¹ ; Jia, Tianli ¹ ; Cai, Dongbo ¹ ; Chen, Junyong ³ ; Wang, Dong ² ; Chen, Shouwen ¹ ;

作者机构： 1.Hubei Univ, Coll Life Sci, Environm Microbial Technol Ctr Hubei Prov, State Key Lab Biocatalysis & Enzyme Engn, Wuhan 430062, Peoples R China

2.Chongqing Acad Agr Sci, Chongqing 400000, Peoples R China

3.Jinan Univ, Zhuhai Hosp, Zhuhai Peoples Hosp, Dept Urol, Zhuhai, Peoples R China

关键词： Bacillus licheniformis; gamma-Aminobutyric acid; Glutamate-derived chemicals; De novo synthesis; Redistribute metabolic flux

期刊名称：METABOLIC ENGINEERING （ 影响因子：6.8； 五年影响因子：7.8 ）

ISSN： 1096-7176

年卷期： 2025 年 88 卷

页码：

收录情况： SCI

摘要： Microbial cell factories (MCFs) have emerged as a sustainable tool for the production of value-added biochemicals. However, developing high-performance MCFs remains a major challenge to fulfill the burgeoning demands of global markets. This study aimed to establish the B. licheniformis cell factory for the cost-effective production of glutamate-derived chemicals by modular metabolic engineering. Initially, the glutamate decarboxylase from E. coli was introduced into B. licheniformis DW2 to construct the artificial gamma-aminobutyric acid (GABA) pathway. By systematically optimizing the central metabolic pathway, boosting the L-Glu synthesis pathway and improving the cofactor NADPH supply, the strain G35/pHY-Pr5u12-gadBE89Q/H465A achieved a remarkable yield of 62.9 g/L of GABA in a 5-L bioreactor, representing the highest yield of 0.5 g/g glucose with a significant 49.3-fold increase. Remarkably, bioinformatics analyses and function verification identified the putative glyoxylate to glycolic acid synthesis pathway and KipR, an inhibitor of the glyoxylate cycle, as the rate- limiting steps in GABA production. Additionally, a versatile and robust platform using engineered B. licheniformis for efficient production of diverse glutamate-derived chemicals was established and the titer of 5-aminolevulinic acid, heme and indigoidine was improved by 5.3-, 4.7- and 1.9-fold, respectively. This study not only facilitates extensive application of B. licheniformis for chemical production, but also sheds light on research to improve the performance of other MCFs.