Integration of (S)-2,3-oxidosqualene enables E. coli to become Iron Man E. coli with improved overall tolerance

被引:5
作者
Sun, Wenjie [1 ,2 ,3 ]
Chen, Yun [1 ,2 ,3 ]
Li, Mengkun [1 ,2 ,3 ]
Shah, Syed Bilal [1 ,2 ,3 ]
Wang, Tianfu [4 ]
Hou, Jin [5 ]
Bai, Linquan [1 ,2 ,3 ]
Feng, Yan [1 ,2 ]
Tan, Zaigao [1 ,2 ,3 ]
机构
[1] Shanghai Jiao Tong Univ, State Key Lab Microbial Metab, Shanghai 200240, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Shanghai 200240, Peoples R China
[3] Shanghai Jiao Tong Univ, Dept Bioengn, Shanghai 200240, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Environm Sci & Engn, Shanghai 200240, Peoples R China
[5] Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong Provin, Peoples R China
来源
BIOTECHNOLOGY FOR BIOFUELS AND BIOPRODUCTS | 2023年 / 16卷 / 01期
基金
中国博士后科学基金; 中国国家自然科学基金; 国家重点研发计划;
关键词
Sterols biosynthesis; (S)-2,3-oxidosqualene; E; coli; Severe stresses; Chemicals production; MICROBIAL CELL FACTORIES; ESCHERICHIA-COLI; BACTERIA; ACID; TEMPERATURE; MEMBRANE; INCREASE;
D O I
10.1186/s13068-023-02444-7
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background While representing a model bacterium and one of the most used chassis in biomanufacturing, performance of Escherichia coli is often limited by severe stresses. A super-robust E. coli chassis that could efficiently tolerant multiple severe stresses is thus highly desirable. Sterols represent a featured composition that distinguishes eukaryotes from bacteria and all archaea, and play a critical role in maintaining the membrane integrity of eukaryotes. All sterols found in nature are directly synthesized from (S)-2,3-oxidosqualene. However, in E. coli, (S)-2,3-oxidosqualene is not present.Results In this study, we sought to introduce (S)-2,3-oxidosqualene into E. coli. By mining and recruiting heterologous enzymes and activation of endogenous pathway, the ability of E. coli to synthesize (S)-2,3-oxidosqualene was demonstrated. Further analysis revealed that this non-native chemical confers E. coli with a robust and stable cell membrane, consistent with a figurative analogy of wearing an "Iron Man's armor"-like suit. The obtained Iron Man E. coli (IME) exhibited improved tolerance to multiple severe stresses, including high temperature, low pH, high salt, high sugar and reactive oxygen species (ROS). In particular, the IME strain shifted its optimal growth temperature from 37 degree celsius to 42-45 degree celsius, which represents the most heat-resistant E. coli to the best of our knowledge. Intriguingly, this non-native chemical also improved E. coli tolerance to a variety of toxic feedstocks, inhibitory products, as well as elevated synthetic capacities of inhibitory chemicals (e.g., 3-hydroxypropionate and fatty acids) due to improved products tolerance. More importantly, the IME strain was effectively inhibited by the most commonly used antibiotics and showed no undesirable drug resistance.Conclusions Introduction of the non-native (S)-2,3-oxidosqualene membrane lipid enabled E. coli to improve tolerance to various stresses. This study demonstrated the effectiveness of introducing eukaryotes-featured compound into bacteria for enhancing overall tolerance and chemical production.
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页数:14
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