Structural Characterization and Biological Activity Screening of Antiviral Tamiflu Biotransformation Products in Probiotic Escherichia coli
프로바이오틱 대장균에 의한 항바이러스제 타미플루 생체전환 생성물의 구조 규명 및 생물학적 활성 스크리닝
- 주제(키워드) 도움말 Gut microbiota , Biotransformation , Oseltamivir , Methanethiol , Sulfur metabolism
- 발행기관 국립강릉원주대학교 일반대학원
- 지도교수 도움말 박현봉
- 발행년도 2025
- 학위수여년월 2026. 2
- 학위명 석사
- 학과 및 전공 도움말 일반대학원 생물학과
- 실제URI http://www.dcollection.net/handler/kangnung/000000012303
- UCI I804:42001-000000012303
- 본문언어 영어
목차 도움말
Ⅰ. Introduction 1
Ⅱ. Materials and Methods 4
1. General experimental procedures 4
2. The bacterial strains used in the study 4
3. Chemicals and kits used in the study 4
4. General metabolite analysis 5
5. Metabolomics date processing and statistical analysis 5
6. Minimum inhibitory concentration test 6
7. Bacterial culture and oseltamivir treatment 6
8. Optimization of larger-scale culture conditions 7
9. Larger-scale culture and metabolome extraction 7
10. Isolation and purification of metabolites 8
11. Substrate feeding studies 8
12. Biomimetic synthesis of the TMT 9
13. Neuraminidase inhibition assay 9
14. Anti-microbial activity assay 10
15. Cell culture 10
16. Cell viability assay 10
Ⅲ. Results 12
1. Determination of sub-lethal growth ranges of oseltamivir against E. coli Nissle 1917 12
2. Metabolomic profiling of E. coli culture supernatant-treated with 1 mM oseltamivir 13
3. Volcano plot analysis for E. coli normal culture and E. coli culture treated with oseltamivir 15
4. TMT production from E. coli culture in the presence of oseltamivir under aerobic condition 17
5. TMT production from E. coli culture in the presence of oseltamivir under anaerobic condition 19
6. Dose-dependent TMT production in the presence of oseltamivir 20
7. Time-course analysis for TMT production 21
8. Examination of TMT production in E. coli treated with four different drugs 22
9. Isolation and purification of TMT metabolites 24
10. Chemical structures of TMT metabolites 25
11. Structure elucidation of TMT metabolite 26
12. Plausible biosynthesis of TMT 30
13. Key methanethiol biosynthetic pathway in bacteria 31
14. TMT stimulation from E. coli culture supplemented with methionine 32
15. Stable-isotope feeding study in E. coli 34
16. Assessment of TMT production in culture conditions of various bacterial strains 35
17. TMT synthesis from oseltamivir and methanethiol 36
18. Experimental verification of the biosynthetic pathway and biomimetic synthesis of TMT 38
19. Chemical structures of acid forms of TMT metabolites 40
20. Structure elucidation of TMT-acid metabolite 41
21. Neuraminidase inhibitory activities of TMT 45
22. Anti-microbial activities of TMT 47
23. Cytotoxicity of TMT 49
Ⅳ. Discussion 50
Ⅴ. Reference 53
