Earticle

초록

영어

A great deal of genomic knowledge has been leaped from a-decade-long efforts, but such achievement has not been transformed into full fruition yet in drug discovery field. With this motivation, we report a systems biological approach for drug targeting and discovery against an opportunistic human pathogen Vibrio vulnificus CMCP6 as an example. This systems biological approach utilizes newly updated genomic information to reconstruct the genome-scale metabolic network of this organism, named VvuMBEL943. Drug targets are selected by metabolite-centric drug targeting method. This metabolite-centric approach for drug targeting is performed by implementing constraints-based flux analysis, which is an optimization-based simulation technique, and predicts so called essential metabolites whose absence disrupts cell growth. Initial set of the predicted essential metabolites was further filtered with additional criteria based on organism specificity and maximal disruptive damage to the cell. Essentiality of final five essential metabolites was experimentally validated by gene knockout experiments. Finally, structural analogs of final five essential metabolites were selected out of large chemical compound library for subsequent high-throughput screening. This systematic approach should facilitate initial stage of drug discovery as well as other human-related diseases. [This work was supported by the Korean Systems Biology Research Project (20100002164) of the Ministry of Education, Science and Technology (MEST) through the National Research Foundation of Korea. Further support by the World Class University Program (R32-2008-000-10142-0) through the National Research Foundation of Korea funded by the MEST is appreciated.]

키워드

저자

• Dokyun NA [ Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea. ]
• Hyun Uk KIM [ Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea. ]
• Tae Yong KIM [ Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea. ]
• Sang Yup LEE [ Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea; Department of Bio and Brain Engineering and BioProcess Engineering Research Center, KAIST, Daejeon 305-701, Republic of Korea. ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국생물공학회 학술대회

• 간기

  반년간

• 수록기간

  1985~2013

• 십진분류

  KDC 476 DDC 576