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The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
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Epoxide Hydrolase-catalyzed Hydrolytic Kinetic Resolution for the Production of Chiral Epoxides

에폭사이드 가수분해효소에 의한 동력학적 가수분해반응을 이용한 광학활성 에폭사이드 생산

  • 이은열 (경성대학교 공과대학 식품공학과)
  • Published : 2002.08.01
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Abstract

Chiral epoxides are valuable intermediates for the asymmetric synthesis of enantiopure bioactive compounds. Microbial epoxide hydrolases (EHs) are newly discovered enzymes and versatile biocatalysts for the preparation of chiral epoxides by enantioselective hydrolysis of cheap and easily available racemic epoxide substrates. EHs are commercially potential biocatalysts due to their characteristics such as high enantioselectivity, cofactor-independent catalysis, and easy-to-Prepare catalysts. In this Paper, recent progresses in biochemistry and molecular biology of EH and developments of novel reaction systems are reviewed to evaluate the commercial feasibility of EH-catalyzed hydrolytic kinetic resolution for the production of chiral epoxides.

광학활성 에폭사이드는 다양한 반응성으로 인하여 고부가 가치 광학활성 의약품 및 농약 합성용 중간체로 널리 이용되고 있다. 광학활성 에폭사이드는 에폭사이드 가수분해효소 (epoxide hydrolase, EH)를 이용하여 저가의 라세믹 기질에 대한 입체선택적 가수분해 반응을 통해 제조할 수 있으며, EH는 유도과정 없이 발현되고 보조인자가 필요 없으며 비교적 효소 안정성도 높아 상업적으로 유용한 효소이다 EH에 대한생화학 및 분자생물학 관련 최근 연구 결과를 바탕으로 촉매활성 증대 및 기질 선택성을 변경시킨 tailer-made형 EH 생촉매 개발이 가능할 것이며, 실규모의 비대칭 광학분할 생물공정 시스템 개발을 통해 EH에 의한 동력학적 가수분해반응을 이용한 광학활성 에폭사이드 생산기술의 상업화가 가능할 것으로 기대된다.

Keywords

References

  1. Sheldon, R. A. (1993), Chirotechnology, Marcel Dekker, New York
  2. Besse, P. and H. Veschambre (1994), Chemical and biological synthesis of chiral epoxides, Tetrah. 50, 8885-8927 https://doi.org/10.1016/S0040-4020(01)85362-X
  3. Archelas A. and R. Furstoss (2001), Synthetic applications of epoxidehydrolases, Curro Opin. Chem. BioI. 5, 112- 119 https://doi.org/10.1016/S1367-5931(00)00179-4
  4. Steimeiber, A. and K. Faber (2001), Microbial epoxide hydrolases for preparative biotransformations, Curro Opin. Biotechnol. 12, 552-558 https://doi.org/10.1016/S0958-1669(01)00262-2
  5. Weijers, C. A. G. M. and J. A. M. de Bont (1999),Epoxide hydrolases from yeasts and other sources: versatile tools in biocatalysis, J. Mol. Catal. B: Enzym. 6, 199-214 https://doi.org/10.1016/S1381-1177(98)00123-4
  6. Zhang, X. M., A. Archelas, and R. Furstoss (1991), Microbiological transformation. 19. Asynunetric dihydroxylation of the remote double bond of geraniol: a unique stereochemical control allowing easy access to both enantiomers of geraniol-6,7-diol, J. Org. Chan. 56, 3814-3817 https://doi.org/10.1021/jo00012a010
  7. Botes, A. L., J. A. Steenkamp, C. A. G. M. Weijers, and M. S. van Dyk (1998), Biocatalytic resolution of 1,2-epoxyoctane using resting cell of different yeast strains with novel epoxide hydrolases activities, Biotechnol. Lett. 20, 421-426 https://doi.org/10.1023/A:1005395817739
  8. Cagnon, J. R., A. L. N. Porto, and A. J. Marsaioli (1999), First evaluation of the brazilian microorganisms biocatalytic potential, Chemosphere, 38, 2237-2242 https://doi.org/10.1016/S0045-6535(98)00442-1
  9. Choi, W. J., E. C. Huh, H. 1. Park, E. Y. Lee, and C. Y. Choi (1998), Kinetic resolution for optically active epoxides by microbial enantioselective hydrolysis, Biotechnol. Tech., 12, 225-228 https://doi.org/10.1023/A:1008825508904
  10. Krenn. W., I. Osprian, W. Kroutil, G. Braunegg, and K. Faber (1999), Bacterial epoxide hydrolases of opposite enantiopreference, Biotechnol. Lett., 21, 687-690 https://doi.org/10.1023/A:1005565108510
  11. Moussou. P., A. Archelas, and R. Furstoss (1998), Microbiologicaltransformations 41. Screening for novel epoxide hydrolase, J. Mol. Catal B: Enzym. 5, 447-458 https://doi.org/10.1016/S1381-1177(98)00007-1
  12. Tang, Y.-F., J.-H. Xu, Q. Ye, and B. Schulze (2001), Biocatalytic preparation of (S)-phenyl glycidyl ether using newly isolated Bacillus megaterium ECU1001 , J. Mol. Catal. B: Enzym. 13, 61-68 https://doi.org/10.1016/S1381-1177(00)00230-7
  13. Van de Werf, M. J., R. A. V. Orm, K. M. Overkamp, Substrate specificity and stereospecificity of limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis DCL14; an enzyme showing sequential and enantioconvergent substrate conversion , Appl. Microbiol. Biotechnol., 52, 380-385 https://doi.org/10.1007/s002530051535
  14. Zocher, F., M. M. Enzelberger, U. T. Bornscheuer, B. Hauer, W. Wohlleben, and R. D. Schmid (2000),Enantioselective hydrolysis of aryl, alicyclic and aliphatic epoxides by Rhodotorula glutinis , J. Biotechnol., 77, 287-292 https://doi.org/10.1016/S0168-1656(99)00225-4
  15. Weijers, C. A. G. M. (1997),Enantioselective hydrolysis of aryl, alicyclic and aliphatic epoxides by Rhodotorula glutinis , Tetrah. Asymm. 8, 639-647 https://doi.org/10.1016/S0957-4166(97)00012-8
  16. Nardini, M., I. S. Ridder, H. J. Rozeboom, K. H. Kalk, R. Rink, D. B. Janssen, and B. W. Dijkstra (1999), The X-ray structure of epoxide hydrolase from Agrobacterium radiobacter ADl, J. BioI. Chem. 274, 14579-14596 https://doi.org/10.1074/jbc.274.21.14579
  17. Zou, J., B. M. Hallberg, T. Bergfors, F. Oesch, M. Arand, S. L. Mowbray, and T. A. Jones (2000), Structure of Aspergillus niger epoxide hydrolase at 1.8 Å resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases, Structure, 8, 111-122. https://doi.org/10.1016/S0969-2126(00)00087-3
  18. Yamada, T., C. Morisseau, J. E. Maxwell, M. A. Argiriadi, D. W. Christianson, and B. D. Hammock (2000), Biochemical Evidence for the Involvement of Tyrosine in Epoxide Activation during the Catalytic Cycle of Epoxide Hydrolase, J. BioI. Chem. 275, 23082-23088 https://doi.org/10.1074/jbc.M001464200
  19. Argiriadi, M. A., C. Morisseau, M. H. Goodrow, D. L. Dowdy, B. D. Hammock, and D. W. Christianson (2000), Binding of Alkylurea Inhibitors to Epoxide Hydrolase Implicates Active Site Tyrosines in Substrate Activation, J. BioI. Chem. 275, 15265-15270 https://doi.org/10.1074/jbc.M000278200
  20. Arand, M., F. Muller, A. Mecky, W. Hinz, P. Urban, D. Pompon, R. Kellner, and F. Oesch (1999), Catalytic triad of microsomal epoxide hydrolase: replacement of Glu404 with Asp leads to a strongly increased turnover rate, Biochem. J. 337, 37-43 https://doi.org/10.1042/0264-6021:3370037
  21. Rink, R., J. H. L. Spelberg, R. J. Pieters, J. Kingma, M. Nardini, R. M. Kellogg, B. W. Dijkstra, and D. B. Janssen (1999), Mutation of Tyrosine Residues Involved in the Alkylation Half Reaction of Epoxide Hydrolase from Agrobacterium radiobacter AD1 Results in Improved Enantioselectivity, J. Am. Chem Soc. 121, 7417-7418. https://doi.org/10.1021/ja990501o
  22. Archelas, A., M. Arand, J. Baratti, and R. Furstoss (1999), French Patent Application No. 9905711; (2000), International Patent Application No. PCT/FR00/01217
  23. Genzel, Y., A. Archelas, O. B. Broxterman, B. Schulze, and R. Furstoss (2001), Microbiological transformations. Part 46: Preparation of enantiopure (S)-2-pyridyloxirane via epoxide hydrolase-catalysed kinetic resolution, Tetrah.Asymm. 11, 3041-3044 https://doi.org/10.1016/S0957-4166(00)00285-8
  24. Genzel, Y., A. Archelas, O. B. Broxterman, B. Schulze, and R. Furstoss (2001), Microbiological Transformations. 47. A Step toward a Green ChemistryPreparation of Enantiopure (S)-2-, -3-, and -4-Pyridyloxirane via an Epoxide Hydrolase Catalyzed Kinetic Resolution, J. Org. Chem. 66, 538-543 https://doi.org/10.1021/jo001406x
  25. Cleij, M., A. Archelas, and R. Furstoss (1998), Microbiological transformations. Part 42: A two-liquid-phase preparative scale process for an epoxide hydrolase catalysed resolution of para-bromo-$\alpha$-methyl styrene oxide. Occurrence of a surprising enantioselectivity enhancement. Tetrah. Asymm. 9, 1839-1842 https://doi.org/10.1016/S0957-4166(98)00180-3
  26. Kronenburg, N. A. E. and J. A. M. de Bont (2001), Effects of detergents on specific activity and enantioselectivity of the epoxide hydrolase from Rhodotorula glutinis, Enzyme Microbial Technol. 28, 210-217 https://doi.org/10.1016/S0141-0229(00)00306-9
  27. Krenn, W., I. Osprian, W. Kroutil, G. Braunegg, and K. Faber (1999), Bacterial epoxide hydrolases of opposite enantiopreference, Biotechnol. Lett. 21, 687-690 https://doi.org/10.1023/A:1005565108510
  28. Lutje Spelberg, J. H., J. E. T. Van Hylckama Vlieg, T.Bosma, R. M. Kellogg, and D. B. Janssen (1999), A tandem enzyme reaction to produce optically active halohydrins, epoxides and diols, Tetrah. Asymm. 10, 2863-2870 https://doi.org/10.1016/S0957-4166(99)00308-0
  29. Mayer, S. F., A. Steinreiber, R. V. A. Orru, and K. Faber (2001), An enzyme-triggered enantio-convergent cascade-reaction, Tetrah. Asymm. 12, 41-43 https://doi.org/10.1016/S0957-4166(01)00010-6
  30. Steinreiber, A., S. F. Mayer, and K. Faber (2001),Biocatalytic asymmetric and enantioconvergent hydrolysis of trisubstituted exiranes, Tetrah. Asymm. 12, 1518-1528 https://doi.org/10.1016/S0957-4166(01)00256-7
  31. Choi, W. J., E. Y. Lee, S. J. Yoon, and C. Y. Choi(1999), Biocatalytic production of chiral epichlorohydrin in organic solvents, J. Biosci. Bioeng. 88, 339-341 https://doi.org/10.1016/S1389-1723(00)80022-5
  32. Choi, W. J., C. Y. Choi, J. A. M. de Bont, and C. A. G. M Weijers (1999), Resolution of 1,2-epoxyhexane by Rhodotorula glutinis using a two-phase membrane bioreactor , Appl. Microbiol. Biotechnol. 53, 7-11. https://doi.org/10.1007/s002530051606
  33. Choi, W. J., Choi, C. Y., J. A. M. de Bont, and C. A. G. M. Weijers (2000), Continuous production of enantiopure 1,2-epoxyhexane by yeast epoxide hydrolase in a two-phase membrane bioreactor, Appl. Microbiol. Biotechnol. 54, 641-646 https://doi.org/10.1007/s002530000451
  34. Botes, A. L., J. Lotter, C. H. Pohl, C. A. Yeates, C. A. Hayward, J. C. Breytenbach, and M. S. Van Dyk (2001), Yeast epoxide hydrolases as biocatalysts for the batch and continuous synthesis of enantiomerically pure epoxides and vic diols, In BioTrans 2001, W. -D. Fessner Ed.; Proc. The $5^{th}$ International Symposium on Biocatalysis and Biotransformation, Darmstadt, p196.
  35. Rink, R., M. Fennema, M. Smids, U. Dehmel, and D. B. Jenssen (1997), Primary Structure and Catalytic Mechanism of the Epoxide Hydrolase from Agrobacterium radiobacter AD1, J. BioI. Chem., 272, 14650-14657 https://doi.org/10.1074/jbc.272.23.14650
  36. Lutje Spelberg, J. H., R. Rink, R. M. Kellogg, and D. B. Janssen (1998), Enantioselectivity of a recombinant epoxide hydrolase from Agrobacterium radiobacter, Tetrah. Asymm. 9, 459-466 https://doi.org/10.1016/S0957-4166(98)00003-2
  37. Arand, M., H. Hemmer, H. Durk, J. Baratti, A. Archelas, and R. Furstoss (1999), Cloning and molecular characterization of a soluble epoxide hydrolase from Aspergillus niger that is related to mammalian microsomal epoxide hydrolase, Biochem. J. 344, 273-280 https://doi.org/10.1042/0264-6021:3440273
  38. Visser, H., S. Vreugdenhil, J. A. M. de Bont, and J. C. Verdoes (2000), Cloning and characterization of an epoxide hydrolase-encoding gene from Rhodotorula glutinis. Appl. Microbiol. Biotechnol. 53, 415-419 https://doi.org/10.1007/s002530051635
  39. Visser, H., J. A. M. de Bont, and J. C. Verdoes (1999), Isolation and Characterization of the Epoxide Hydrolase-Encoding Gene from Xanthophyllomyces dendrorhous, Appl. Environ. Microbiol. 65. 5459-5463