KSBB Journal

The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
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Enantioselective Hydrolysis for the Precursor of Azole-containing Compounds using Acinetobacter sp. SY-01 Lipase and Increase of Enantioselectivity by the Removal of Reaction Products

Acinetobacter sp. SY-01 Lipase를 이용한 아졸계 화합물 전구체에 대한 광학선택적 가수분해 반응과 생성물 제거에 의한 광학선택성 증가

  • 윤문영 (한국과학기술연구원 의학화학연구센터, 동국대학교 생명화학공학과) ;
  • 신평균 (한국과학기술연구원 수질환경연구센터) ;
  • 정찬성 (한국과학기술연구원 의약화학연구센터) ;
  • 박정극 (동국대학교 생명화학공학과)
  • Published : 2003.02.01
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Abstract

Screening of a strain was carried out to produce an enantioselective lipase toward the precursor of ltraconazole as azole-containg compounds, which are well known as antifungal drug agents. An Acinetobacter sp. SY-01 strain which can selectively hydrolyze the racemic substrates was isolated and the racemic substrate was resolved to the S-ester in 95.6% enantiomeric excess after 74.8% hydrolysis. The optimum temperature and pH for the conversion were $50^{\circ}C$, pH 7.0. However, the temperature and pH had no effect on the enantiomeric excess. Addition of solvents decreased the conversion and slightly increased the enantiomeric excess. However, the kind of solvents had no effect on enantiomeric excess. The substrate concentration decrease enantiomeric excess and this is confirmed by the products generated from hydrolysis, and also enantiomeric excess could be increased by the removal of reaction products.

항진균제로 잘 알려진 아졸계 화합물인 이트라코나졸 전구체에 대한 광학선택성 lipase 생산균주 탐색을 수행하였다. 본 라세믹 기질을 선택적으로 가수분해하는 lipase 생산균주 인 Acinetobacter sp. SY-01 를 분리하였고, 효소 가수분해반응을 수행한 결과 본 라세믹 기질은 전환율이 74.8%에 도달하였을 때 95.6%의 ee값을 가지는 S-ester로 분할되었다. 전환율은 온도 $50^{\circ}C$, pH 7.0에서 가장 높게 나타났고, 광학선택성은 온도, pH에 의해 영향을 받지 않았다. 용매의 첨가에 의해 전환율은 감소하였으나 광학선택성은 약간 증가하였다. 기질농도가 증가함에 따라 광학선택성은 감소하였고, 이것은 가수분해반응 생성물에 의한 영향으로 확인되어 반응 생성물을 제거함으로써 광학선택성을 증가시킬 수 있었다.

Keywords

References

  1. Trends Biochem. Sci. v.14 Nonchiral, homochiral and composite chiral drugs Ariens, E. J.
  2. CHEMTECH v.12 Drug chirality-scale-up, manufacturing, and control Federsel, H. J.
  3. J. Antimicrobial Chemotheraphy v.37 Drug chirality: a consideration of the significance of the stereochemistry of antimicrobial agent Hutt, A. J.;J. O'Grady
  4. CHEMTECH v.3 Chiral drugs : The coming revolution Deutsch, D.H.
  5. Chem. Eng. News v.6 no.15 FDA issues flexible policy on chiral drugs Borman, S.
  6. US Patent No. 5,474,997 Methods and compositions of (2R, 4S) Itraconazole for treating fungal yeast and dermatophyte infections Gray, N. M.;R. L. Woosley
  7. US Patent No. 5,952,502 2R, 4S, R, S- and 2S, 4R, R, S-Hydroxyitraconazole McCullough, J. R.;C. H. Senanayake;G. J. Tanoury;Y. Hohg;P. Koch
  8. Korean J. Biotechnol. Bioeng. v.15 no.5 Chiral resolution using enzymes Lee, E. G.;B. H. Chung
  9. Korean J. Biotechnol. Bioeng. v.16 no.3 Development of hollowfiber reactor system for the production of chiral 1,2-expoxy-7-octene by microbial enantioselective hydrolysis reaction Lee, E. Y.;H. S. Kim
  10. Tetrahedron v.42 Enzymes in organic synthesis Jones, J. B.
  11. Enzyme Micro. Technol. v.15 Enzymes in the synthesis of chiral drugs Margolin, A.
  12. Chem. Rev. v.92 The biocatalytic approach to the preparation of enantiomerically pure chiral building blocks Santoniello, E.;P. Ferraloschi;P. Grisent;A. Monzouchi
  13. Enzyme Microb. Technol. v.17 Enantioselective hydrolysis of ethyl 2-hydroxyalkanoates by an extracellular esterase from a Bacillus sphaericus strain Michael, A. J.;P. L. David;A. B. Lynne
  14. J. Ferm. Bioeng. v.83 no.1 Process development for the production of the (S)-acid precursor of a novel elastase inhibitor(L-694, 458) through the lipasecatalyzed kinetic resolution of a β-lactam benzyl ester Christopher, R.;J. C. Raymond;S. A. Joseph;P. Victor;W. H. Frederick;G. Randolph;C. Michel
  15. Biotech. Bioeng. v.64 no.2 Optimizing lipase activith, enantioselectivity, and stability with medium engineering and immobilization for β-blocker synthesis Mohapatra, S. C.;J. T. Hsu
  16. Tetrahedron v.51 no.32 Structure of solvent affects enantioselectivity of lipase-catalyzed transesterification Kaoru, N.;K. Masamichi;O.Atsuyoshi
  17. J. Ferment. Bioeng. v.78 Production of optically active 3-phenylglycidic acid ester by the lipase from Serratia marcescens on a hollow-fiber membrane reactor Matsumae, H.;M. Furui;T. Shibatani;T. Tosa
  18. J. Am. Chem. Soc. v.107 Resolution of racemic mixtures via lipase catalysis in organic solvents Kirchner, G.;M. P. Scollar;A. M. Klibanov
  19. Kor. J. Appl. Microbiol. Biotechnol. v.24 no.2 Preparation of (S)-3-acetoxy-2-methylpropanol with lipase Seu, Y. B.;Y. C. Su;K. D. Lee
  20. Synthetic Communications v.28 no.23 Lipase-catalyzed kinetic resolution of the racemic mixtures of 1-aryloxy-3-nitrato-and 1-aryloxy-3-azido-2-propanols Beata, P.;R. Justyna;Plenkiewicz
  21. Biotech. Bioeng. v.53 no.3 Phosphate uptake kinetics by Acinetobacter isolates Anneli S.-L. P
  22. Biotech. Bioeng. v.62 no.3 Effect of oxygen transfer on lipase production by Acinetobacter radiorestistens Chen, J. Y.;C. H Wen;T. L. Chen
  23. Manual of Methods for General Bacteriology Gerhardt, P.
  24. JAOACS v.69 Screening of lipase activities with cultures from the agricultural research services culture collection Hou, C. T.;T. M. Johnston
  25. Clin. Chim. Acta. v.13 A specific method for serum lipase determination Tietz, N. W.;E. A. Fiereck
  26. J. Am. Chem. Soc. v.104 Quantitative analyses of biochemical kinetic resolution of enantiomers Chen, C. H.;Y. Fujimoto;G. Girdaukas;C. J. Sih
  27. J. Am. Chem. Soc. v.110 Control of enzyme enantioselectivity by the reaction medium Sakurai, T.;A. L. Margolin;A. J. Russell;A. M. Klibanov
  28. Tetrahedron v.51 no.32 Structure of solvent affects enantioselectivity of lipase-catalyzed transesterification Nakamura, K.;M. Kinoshita;A. Ohno
  29. Tetrahedron v.52 no.15 Factors influencing enantioselectivity of lipase-catalyzed hydrolysis Kinoshita, M.;A. Ohno
  30. Tetrahedron v.52 no.13 Influence of organic solvents on enzyme chemoselectivity and their role in enzyme-substrate interaction Ebert, C.;L. Gardossi;P. Linda;R. Vesnaver