표제지
목차
Abbreviation 10
국문초록 12
Ⅰ. 서론 14
Ⅱ. 실험 재료 및 방법 18
1. 실험 재료 18
1.2. 실험 기구 및 시약 19
2. 실험 방법 22
2.1. 배양 및 추출 방법 22
2.2. 분석시료 제조 23
2.3. LC-MS/MS 측정 24
2.4. 데이터 가공 24
2.5. 추출 및 분획 26
2.6. 항진균 및 항세균 활성 평가 29
Ⅲ. 실험 결과 및 고찰 30
1. Penicillium의 후성유전조절제에 의한 대사 변화 30
1.1. 30종의 Penicillium 스크리닝 결과 30
1.2. 재현성 및 대사산물의 생산량 변화 결과 51
2. HDAC inhibitor-Penicillium sp.97 분리 연구 54
2.1. 타겟 분리 및 화합물의 구조 규명 54
2.2. 항진균 및 항세균 활성 평가 63
Ⅳ. 결론 64
Ⅴ. 참고문헌 66
ABSTRACT 71
Table 1. Previous study of epigenetic modulation for fungi 16
Table 2. Penicillium strain list 18
Table 3. ¹H, ¹³C NMR data of compound 1, 2 (methanol-d₄) 28
Table 4. Correlation between the increase in metabolite MS intensity and the yield 32
Table 5. Metabolites reduced in production by epigenetic modulators 38
Table 6. Metabolites increased in production by epigenetic modulators 43
Figure 1. Epigenetic modulator mechanism 15
Figure 2. Data processing workflow 24
Figure 3. Molecular Networking guided isolation of P. sp.97 27
Figure 4. Penicillium-epigenetic modulator pair metabolites change comparison 31
Figure 6. In the P. jejuense, increased production of metabolites 45
Figure 7. In the P. sp.97 and P. jejuense, unidentified metabolites with increased production 46
Figure 8. In the Penicillium jejuense-epigenetic modulator pair, unknown pathway 48
Figure 9. In the P. jejuense, biosynthetic pathway of identified metabolites 49
Figure 10. In the P. sp.97, biosynthetic pathway of unknown metabolites 50
Figure 11. first reproducibility and foldchange of 5 strains 52
Figure 12. second reproducibility and foldchange of 5 strains 53
Figure 13. Identification of the structure of the compound 1, location of increase in production and reproducibility of compound 1 in volcanic plot 54
Figure 14. ¹H NMR (500 MHz) and ¹³C NMR (125 MHz) spectrum of compound 1 in methanol-d₄ 56
Figure 15. HSQC spectrum of compound 1 in methanol-d₄ 57
Figure 16. HMBC spectrum of compound 1 in methanol-d₄ 57
Figure 17. ¹H-¹H COSY spectrum of compound 1 in methanol-d₄ 58
Figure 18. Identification of the structure of the compound 2, location of increase in production and reproducibility of compound 2 in volcanic plot 59
Figure 19. ¹H NMR (500 MHz) and ¹³C NMR (125 MHz) spectrum of compound 2 in methanol-d₄ 60
Figure 20. HSQC spectrum of compound 2 in methanol-d₄ 61
Figure 21. HMBC spectrum of compound 2 in methanol-d₄ 61
Figure 22. ¹H-¹H COSY spectrum of compound 2 in methanol-d₄ 62