数字农科院2.0

Genome-scale Metabolic Modeling Guided Escherichia coli Engineering for De Novo Biosynthesis of Chrysanthemic Acid

文献类型： 外文期刊

作者： Yu, Jiangpeng;Cheng, Kelin;Qu, Shenyang;Wang, Jie;Wang, Xun;Zhao, Cheng;Li, Wei

作者机构：

关键词： （1-1-1）cell factory;chrysanthemic acid;debranching strategy;E. coli;Genome-scale metabolic model

期刊名称： ADVANCED SCIENCE

ISSN：

年卷期： 2025 年

页码：

收录情况： SCIE（2025版） ; ; EI（2025版）

摘要： Chrysanthemic acid is an unconventional monoterpene moiety of the natural pesticide pyrethrins with notable anti-insect activity, making its industrial biosynthesis a promising avenue for sustainable agriculture. Here, an E. coli cell factory is designed and build for highly efficient chrysanthemic acid production guided by Genome-scale metabolic models (GEM). The biosynthetic pathway is reconstructed and simulated the metabolic changes caused by exogenous modules are simulated. A key metabolic branch point catalyzed by ispA is identified by this model, and inhibiting its expression using synthetic small RNA redirected the metabolic flux, resulting in the titers of precursor chrysanthemol and chrysanthemic acid increasing by 162% and 59%, respectively. The effect of the expression level of downstream dehydrogenases on chrysanthemic acid titer is also predicated using GEM, and the further optimization of copy number for dehydrogenase genes led to a notably 570% increase in chrysanthemic acid titer experimentally. By integrating the debranching strategy with copy number optimization, a record chrysanthemic acid titer 141.78 mg L-1 is achieved in a bioreactor. The work seamlessly integrated in silico modeling optimization with wet-lab practices that significantly enhance target metabolite titer through metabolic network engineering, offering a new route for constructing efficient cell factories for natural bioproducts.

分类号：

  • 相关文献

[1]In silico analysis and recombinant expression of BamA protein as a universal vaccine against Escherichia coli in mice. Guan, Qingfeng,Wang, Xiao,Wang, Xiumin,Teng, Da,Wang, Jianhua,Guan, Qingfeng,Wang, Xiao,Wang, Xiumin,Teng, Da,Wang, Jianhua.

[2]Accumulation of antibiotics and heavy metals in meat duck deep litter and their role in persistence of antibiotic-resistant Escherichia coli in different flocks on one duck farm. Zhang, X. T.,Ji, X.,Zou, X. T.,Yao, W.,Lin, Y.,Zhao, W.,Shi, Z. D.,Gu, H. R.,Gong, J. S..

[3]Trends in Frequency, Potential Risks and Antibiogram of E. coli Isolated from Semi-Intensive Dairy Systems. Muhammad Ahsan Anwar,Sidra Aziz,Khurram Ashfaq,Amjad Islam Aqib,Muhammad Shoaib,Muhammad Aamir Naseer,Mughees Aizaz Alvi,Iqra Muzammil,Zeeshan Ahmad Bhutta,Huma Sattar,Arslan Saleem,Tean Zaheer,Fakhara Khanum,Asif Mahmood. 2022

[4]Expression Pattern of Cathelicidins in Dairy Cows During Endometritis and Role of Bovine Endometrial Epithelial Cells in Production of Cathelicidins. Yajuan Li,Xiaoyu Ma,Jie Yang,Xiaohu Wu,Zuoting Yan,Baoxiang He. 2021

[5]Design of a Controlled-Release Delivery Composite of Antibacterial Agent Gatifloxacin by Spherical Silica Nanocarrier. Xueping Guo,Wenjing Mo,Dingyang Zhang,Yurong Wang,Fang Cao,Tianyun Zhai,Wenhua Rao,Xiong Guan,Lei Xu,Xiaohong Pan. 2022

[6]High uptake of citrus essential oil-loaded zein particles into E. coli tuned by the wet-crosslinked folic acid. Feilong Yang,Chengying Zhao,Liping Feng,Yanqi Wang,Mengyu Ma,Vincenzo Fogliano,Jinkai Zheng,Ashkan Madadlou. 2023

[7]Multidrug-Resistant Escherichia coli Isolate of Chinese Bovine Origin Carrying the blaCTX-M-55 Gene Located in IS26-Mediated Composite Translocatable Units. Weiwei Wang,Xiaojuan Wei,Safia Arbab,Lingyu Wu,Ningning Lu,Qiqi Zhu,Yubin Bai,Jiyu Zhang. 2023

[8]Genomic insights into resistome, virulome, and mobilome as organic contaminants of ESKAPE pathogens and E. coli recovered from milk, farm workers, and environmental settings in Hainan, China. Ruochen Hao,Muhammad Shoaib,Minjia Tang,Zongxi Cao,Guangliang Liu,Yan Zhang,Shengyi Wang,Ruofeng Shang,Hongjuan Zhang,Wanxia Pu. 2024

[9]Recent advances in genome-scale engineering in Escherichia coli and their applications. Gao H.,Qiu Z.,Wang X.,Zhang X.,Zhang Y.,Dai J.,Liang Z.. 2024

[10]Mechanisms of Baicalin Alleviates Intestinal Inflammation: Role of M1 Macrophage Polarization and Lactobacillus amylovorus. Zhang, Shunfen,Zhong, Ruqing,Zhou, Miao,Li, Kai,Lv, Huiyuan,Wang, Huixin,Xu, Ye,Liu, Dadan,Ma, Qiugang,Chen, Liang,Zhang, Hongfu. 2025

[11]Dimetridazole potentiates cefotaxime against multidrug-resistant E. coli via membrane disruption and fatty acid composition. Xiaojuan Wei,Weiwei Wang,Safia Arbab,Qing Wang,Yubin Bai,Jiyu Zhang. 2025

[12]Antibacterial activity and mechanism of Stevia extract against antibiotic-resistant Escherichia coli by interfering with the permeability of the cell wall and the membrane. Xu Chen,Lan Kun Yi,Yu Bin Bai,Ming Ze Cao,Wei Wei Wang,Zi Xuan Shang,Jia Jing Li,Mei Li Xu,Li Fei Wu,Zhen Zhu,Ji Yu Zhang. 2024

[13]A rapid detection method for Escherichia coli O157:H7 and Salmonella Typhimurium in food based on the combination of loop-mediated isothermal amplification and hybridization chain reaction. Kunpeng Zhu,Jiaqi Kong,Fei Lao,Liang Zhao,Ailiang Chen,Hui Li. 2025

[14]Exploring the toxicity of bisphenol A and its analogue bisphenol S-MPE to Escherichia coli K12 from integrated AutoQSAR and transcriptomics analysis. Pengyu Chen,Yuxi Hu,Zhichao Dou,Xuemin Feng,Na Zhao,Chenglong Ban,Qiang Wang. 2025

[15]Antimicrobial resistance patterns and high prevalence of the mcr-1 gene in pathogenic Escherichia coli from diseased poultry. A. Khan,A. Ihsan,F. Ullah,O. Ullah,S. Nawaz,M. I. Khan,K. J. Alzahrani,K. F. Alshrafi,T. Ali,A. Qadeer. 2025

作者其他论文 更多>>