文献类型： 外文期刊
作者： Chen, Yi-Ling 1 ; Liu, Xu 3 ; Zhang, Li-Zhan 3 ; Yang, Ji-Shuai 3 ; Guo, Wei-Ke 1 ; Zheng, Shuang 1 ; Wang, Jia-Le 1 ; Wu, Fu-Qing 1 ; Yan, Xu 1 ; Wu, Qiong 1 ; Chen, Guo-Qiang 1 ;
作者机构： 1.Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China
2.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China
3.PhaBuilder Biotechnol Co Ltd, Beijing 101309, Peoples R China
4.Chinese Acad Agr Sci, State Key Lab Anim Nutr, Inst Anim Sci, Beijing 100193, Peoples R China
5.Tsinghua Univ, Dept Chem Engn, Key Lab Ind Biocatalysts, Minist Educ, Beijing 100084, Peoples R China
6.Tsinghua Univ, Ctr Synthet & Syst Biol, Beijing 100084, Peoples R China
关键词： cell sizes; ClpXP; Halomonas; morphology engineering; mreB; next generation industrial biotechnology; PHB
期刊名称：ADVANCED SCIENCE （ 影响因子：14.1； 五年影响因子：15.6 ）
ISSN：
年卷期： 2025 年 12 卷 14 期
页码：
收录情况： SCI
摘要： Most bacterial cells are 1-2 microns in size, limiting intracellular products like polyhydroxyalkanoates (PHA) accumulation. Cell size is regulated by key genes such as mreB and minCD, which encode cellular skeleton protein and control cell fission ring location, respectively. Their expression changes significantly affect microbial growth. This study successfully redesigns the ClpXP protein degradation system by deleting the sspB gene and using mutated SsrA tags with different degradation rates to control MreB degradation. Dynamic degradation of MreB allows non-model bacterium Halomonas bluephagenesis to grow normally and increase cell size simultaneously. Combined with overexpression of minCD, H. bluephagenesis with progressive MreB degradation increases the cell size further, albeit with a reduced growth rate. H. bluephagenesis CYL0307, with the PHB granule-associated protein PhaP1 deleted and phaABRe overexpressed in the MreB-degraded strain, increases cell volume more than nine times compared to the original strain. CYL0307 produces 149 g L-1 cell dry weight containing 82% PHB after 44 h in a 5000 L bioreactor, with cells containing single large PHB granules, simplifying recovery and purification. These results provide a post-translational gene regulation method in H. bluephagenesis and a strategy for enhancing PHB production via morphological engineering.
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