세균의 지방산 생합성 효소 (Enoyl-Acyl Carrier Protein Reductase, Fabl)를 저해하는 새로운 항균물질의 스크리닝

• 영문명: Screening of New Antibiotics Inhibiting Bacterial Enoyl-Acyl Carrier Protein Reductase (Fabl)
• 발행기관: 대한약학회
• 저자명: 곽진환(Jin Hwan Kwak)
• 간행물 정보: 『약학회지』제46권 제1호 (2002년), 24~29쪽, 전체 6쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2002.02.28

영문 초록

Enoyl-Acyl Carrier Protein Reductase (Fabl) of bacteria is known as an important target for new antibacterial drugs and plays a determinant role in completing cycles of elongation in type-ll tatty acid synthase system. In this study; a fabI gene from Staphylococcus aureus 6538p was cloned in Pet-l4b vector and Fabl protein was over-produced in Escherichia coli BL2l (DE3). NH2-terminal His-tagged Fabl protein was purified by nickel-nitrilotriacetic acid (Ni-NTA) metal- affinity chromatography. Purified 6xHis-tagged Fabl showed a catalytic activity on trans-2-octenoyl-N-acetylcysteamine by utilizing NADPH as a cofactor. For the discovery of new Fabl inhibitors from chemical libraries, a target-oriented screening system using a 96-well plate was developed. About 10,000 chemical libraries from Korea Chemical Bank were tested in this screening system, and 26 chemicals (0.25%) among them showed an inhibitory activity against Fabl enzyme. This result showed that a new screening system can be used for the discovery of new Fabl inhibitors.

키워드

Bacterial Enoyl-Acyl Carrier Protein Reductase(FabI) Antibiotics Screening Essential Gene Target.