| 학회 |
한국공업화학회 |
| 학술대회 |
2019년 봄 (05/01 ~ 05/03, 부산 벡스코(BEXCO)) |
| 권호 |
23권 1호 |
| 발표분야 |
(생물공학) 생리활성 이차대사산물 생산 최신동향 |
| 제목 |
Discovery of hidden biosynthetic routes to gentamicin and novel analogs with premature termination codon readthrough activity |
| 초록 |
Gentamicin, an aminoglycoside antibiotic produced by Micromonospora echinospora, is widely used to treat bacterial infections. Despite its biological significance, the exact biosynthetic route has remained unclear. We have elucidated the three hidden biosynthetic pathways leading to gentamicin B through in vitro reconstitution and discovered seven unknown minor intermediates. In addition, the crystal structure of the key enzyme detailed the low production of gentamicin B caused by narrow substrate specificity in the wild-type producer. The new gentamicin analogs showed that PTC readthrough activity similar to the natural aminoglycoside G418 was maintained, but the in vitro nephrotoxicity was reduced. This detailed understanding of gentamicin biosynthesis will be enable to use for expanding aminoglycoside structural diversity. |
| 저자 |
반연희, 윤여준
|
| 소속 |
이화여자대 |
| 키워드 |
Gentamicin biosynthesis; Novel analogs; PTC readthrough activity
|
| E-Mail |
|
