Molecular Dynamics Simulation Study of Lipase-catalyzed Esterification of Structural Butanol Isomers in Supercritical Carbon Dioxide

초임계 이산화탄소에서 리파아제-효소를 이용한 부탄올 구조이성질체의 에스테르화 반응의 분자 동역학 연구

  • Kwon, Cheong-Hoon (Department of Chemical and Biological Engineering, Korea University) ;
  • Jeong, Jeong-Yeong (Department of Chemical and Biological Engineering, Korea University) ;
  • Song, Kwang Ho (Department of Chemical and Biological Engineering, Korea University) ;
  • Kim, Seon Wook (The School of Electrical Engineering, Korea University) ;
  • Kang, Jeong-Won (Department of Chemical and Biological Engineering, Korea University)
  • 권정훈 (고려대학교 화공생명공학과) ;
  • 정정영 (고려대학교 화공생명공학과) ;
  • 송광호 (고려대학교 화공생명공학과) ;
  • 김선욱 (고려대학교 전기전자전파공학부) ;
  • 강정원 (고려대학교 화공생명공학과)
  • Received : 2007.11.14
  • Accepted : 2007.11.27
  • Published : 2007.12.10

Abstract

Lipase-catalyzed esterification of structural butanol isomers and n-butyric acid was investigated in supercritical carbon dioxide. The experiments were performed in a high pressure cell for 5 hrs with a stirring rate of 150 rpm at 323.15 K and 130 bar. The Candida Antarctica lipase B (CALB) was used in whole system as a catalyst. The experimental results were analyzed by GC-FID using a INNOWax capillary column. The conversion yield and the tendency of the esterification in supercritical carbon dioxide were compared with estimated results by molecular dynamics simulation. Based on the Ping-Pong Bi-Bi mechanism with competitive inhibition, each step of the reaction was optimized; using this result the transition state was predicted. Conformational preference of isomers was also analyzed using molecular dynamics simulations. This kind of approach will be further extended to the prediction of enzyme-catalyzed reactions using computers.

Acknowledgement

Supported by : 한국학술진흥재단

References

  1. J. F. Cramer, M. S. Dueholm, S. B. Nielsen, D. S. Pedersen, R. Wimmer, and L. H. Pedersen, Enzyme Microb. Technol., 41, 346 (2001)
  2. M. M. Shamel, K. B. Ramachandran, M. Hasan, and S. Al-Zuhair, Biochem. Eng. J., 34, 228 (2007)
  3. A. Chojnacka, R. Obara, and C. Wawrzenczyk, Tetrahedron:Asym- metry, 18, 101 (2007)
  4. A. J. Mulholland, Drug Discov. Today, 10, 1393 (2005) https://doi.org/10.1016/S1359-6446(05)03611-1
  5. D. F. Taber, M. Xu, and J. C. Hartnett, J. Am. Chem. Soc., 124, 13121 (2002) https://doi.org/10.1021/ja020816v
  6. I. Vallikivi, Ü. Lille, A. Lookene, A. Metsala, P. Sikk, V. Tõugu, H. Vija, L. Villo, and O. Parve, J. Mol. Catal. B: Enzym, 22, 279 (2003) https://doi.org/10.1016/S1381-1177(03)00043-2
  7. S. H. Krishna and N. G. Karanth, Biochimica et Biophysica Acta, 1547, 262 (2001) https://doi.org/10.1016/S0167-4838(01)00194-7
  8. S. Raza, L. Fransson, and K. Hult, Protein Science, 10, 329 (2001) https://doi.org/10.1110/ps.33901
  9. J. Gao, S. Ma, D. T. Major, K. Nam, J. Pu, and D. G. Truhlar, 2006. Chem. Rev., 106, 3188 (2006) https://doi.org/10.1021/cr050293k
  10. I. Vallikivi, L. Fransson, K. Hult, I. Järving, T. Pehk, N. Samel, V. Tugu, L. Villo, and O. Parve, J. Mol. Catal. B: Enzym., 35, 62 (2005) https://doi.org/10.1016/j.molcatb.2005.05.008
  11. M. J. Field, J. Comput. Chem., 23, 48 (2002) https://doi.org/10.1002/jcc.1156
  12. C. I. Sainz-Diaz, G. Wohlfahrt, E. Nogoceke, A. HernAndez- Laguna, Y. G. Smeyers, and U. Menge, Theochem-J. Mol. Struct., 390, 225 (1997)
  13. G. Monard, X. Prat-Resina, A. González-Lafont, and J. M. Lluch, Inter. J. Quantum Chemistry, 93, 229 (2003)
  14. M. Garcia-Viloca, D. G. Truhlar, and J. Gao, Biochemistry, 42, 13558 (2003)
  15. C. H. Kwon, D. Y. Shin, J. H. Lee, S. W. Kim, and J. W. Kang, J. Microbiol. Biotechnol, 17, 1098 (2007)
  16. J. Uppenberg, M. T. Hansen, S. Patkar, and T. A. Jones, Structure, 2, 293 (1994)
  17. HyperChem Release 7.0 for windows. Hypercube Inc. (2002)
  18. A. Magnusson, Thesis, School of Biotechnology, Royal Institute of Technology, Sweden (2005)
  19. CAChe Workspace Ver. 6.1. Fujitsu, (2003)
  20. J. J. P. Stewart, J. Comput. Chem., 10, 209 (1989) https://doi.org/10.1002/jcc.540100208
  21. Discovery Studio Modeling version 1.7. Accelrys Inc. (2007)
  22. S. K. Son, Master Thesis, Korea University, Seoul, Korea (2006)