화학공학소재연구정보센터
Korean Chemical Engineering Research, Vol.51, No.6, 716-726, December, 2013
효소를 이용한 아실화 반응의 최근 동향과 전망
Recent Developments and Prospects in the Enzymatic Acylations
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초록
가수분해 효소(혹은 아실전이효소)를 이용한 알콜과 아민의 아실반응은 에스터의 가수분해 반응(hydrolysis, deacylation)과 더불어 효소를 이용한 유기합성 반응에서 이미 잘 확립된 기술로서, 산업체에서 제약의 합성이나 고분자의 합성에서 널리 응용되고 있다. 이러한 효소를 이용한 아실화 반응은 주로 열역학적인 제한으로 인해 그동안 대부분이 주로 유기용매에서 이루어지고 있다. 최근 들어서, 수용액에서 아실화반응을 전이효소를 이용하여 효율적으로 할 수 있다는 보고와 함께 그 반응 기제에 대한 연구들이, X-ray 구조와 이러한 반응을 가능하게 하는 효소의 단백질 서열 비교 연구, 그리고 계산 화학에 의한 효소의 설계 연구등을 통해 새롭게 밝혀지고 있다. 본 총설에서는 효소를 이용한 아실화반응을 유기용매와 수용액에서의 수행함에 있어서 장단점을 비교해 보면서, 앞으로의 전망도 함께 제시하고자 한다. 특별히 다양한 천연물들의 구조 변화에 아실화 반응 생체촉매를 사용할 수 있는 가능성에 대해 살펴볼 것이다.
Enzymatic acylations catalyzed by hydrolytic enzymes, along with enzymatic hydrolysis, are established reactions in the synthesis of fine chemicals such as chiral intermediates and polymerizations in the industry. Those reactions have been carried out mostly in organic media due to the thermodynamic limitations. Recently, there have been reports on enzymatic acylations in aqueous media. They have dealt with the elucidation of reaction mechanisms of hydrolases and acyl transferases based on their X-ray structures, homology comparison of the two kinds of enzymes, substrate engineering of acyl donors and computational design of acyl transferases for enzymatic acylations in aqueous media. Enzymatic acylations play an important role in the combinatorial synthesis of natural products such as polyketides and nonribosomal peptides. In this review, the historic developments of enzymatic acylations and industrial examples are described briefly. In addition, recent developments of enzymatic acylations in the modification of natural products and their prospects will be discussed.
  1. Faber K, “Biotransformations in Organic Chemistry,” Springer (1997)
  2. Roberts SM, J. Chem. Soc., Perkin Trans., 1, 157 (1998)
  3. Turner NJ, O'Reilly E, Nature Chem. Biol., 9, 285 (2013)
  4. Liese A, Seelback K, Wandrey C, Industrial Biotransformations, Wiley-VCH, Weinheim (2006)
  5. Strohmeier GA, Pichler H, May O, Gruber-Khadjawi M, Chem. Rev., 111(7), 4141 (2011)
  6. Schmid A, Dordick JS, Hauer B, Kiener, Wubbolts AM, Witholt B, Nature., 409, 258 (2001)
  7. Bornscheuer UT, Huisman GW, Kazlauskas RJ, Lutz S, Moore JC, Robins K, Nature, 485(7397), 185 (2012)
  8. Park D, Lee J, Korean J. Chem. Eng., 30(5), 977 (2013)
  9. Min EJ, Lee ES, Korean Chem. Eng. Res., 50(2), 257 (2012)
  10. McLachlan MJ, Sullivan RP, Zhao H, “Directed Enzyme Evolution and High-Throughput Screening in Directed Enzyme Evolution and High-Throughput Screening,” in Biocatalysis for the Pharmaceutical Industry : Discovery, Development, and Manufacturing, eds. Tao GQ, Lin AL, Ch. 3, 45-64 John Wiley & Sons (2009)
  11. Boersma YL, Droge MJ, Quax WJ, FEBS J., 274, 2181 (2007)
  12. Wang M, Si T, Huimin Z, Biores. Technol., 115, 117 (2012)
  13. Quin MB, Schmidt-Dannert C, ACS Catal., 11017 (2011)
  14. Patel RN, Coord. Chem. Rev., 252, 659 (2008)
  15. Zaks A, Klibanov AM, Science., 224, 1249 (1984)
  16. Zaks A, Klibanov AM, Proc. Natl. Acad. Sci. USA., 82, 3192 (1985)
  17. Riva S, Chopineau J, Kieboom APG, Klibanov AM, J. Am.Chem. Soc., 110, 584 (1988)
  18. Kobayashi T, Biotechnol. Lett., 33(10), 1911 (2011)
  19. Paravidino M, Hanefeld U, Green Chem., 2651 (2011)
  20. Sheldon RA, Green Chem., 9, 1273 (2007)
  21. Barbayianni E, Kokotos G, ChemCatChem., 4, 592 (2012)
  22. Schoevaart R et al., Spec. Chem. Mag., 27(8), 38 (2007)
  23. Miyazawa K, Yoshida N, “Process for Producing Optically Active α-hydroxyesters Using Lipase PS,” UP 5248610 (Chisso, Japan) (1993)
  24. Kobayashi S, Encyc. Polym. Sci.Tech., “Enzymatic Polymerization,” (2011)
  25. Kobayashi S, Macromol. Rapid Commun., 30(4-5), 237 (2009)
  26. OECD Primer, “The Application of Biotechnology to Industrial Sustainability-a Primer,” Organization for Economic Co-operation and Development (OECD) (2001)
  27. Binns F, Taylor A, “Enzymatic Synthesis,”WO 1994012652 (Baxenden Chemicals, UK) (1994)
  28. Binns F, Harffey P, Roberts SM, Taylor A, J. Polym. Sci. A: Polym. Chem., 36(12), 2069 (1998)
  29. McCabe RW, Taylor A, Green Chem., 6, 151 (2004)
  30. Gross RA, Ganesh M, Lu W, Trends Biotechnol., 28, 435 (2010)
  31. Park HG, Do JH, Chang HN, Biotech. Bioproc. Eng., 8, 1 (2003)
  32. Park OJ, Jeon GJ, Yang JW, Enzyme Microb. Technol., 25(3-5), 455 (1999)
  33. Park OJ, Kim DY, Dordick JS, Biotechnol. Bioeng., 70(2), 208 (2000)
  34. John G, Zhu G, Li J, Dordick JS, Angew. Chem. Int. Ed., 45, 4772 (2006)
  35. Jadhav SR, Vemula PK, Kumar R, Raghavan SR, John G, Angew. Chem. Int. Ed., 49, 7695 (2010)
  36. Jiang Y, Morley KL, Schrag JD, Kazlauskas RJ, ChemBioChem., 12, 768 (2011)
  37. Brenneis R, Baeck B, Biotechnol. Lett., 34(8), 1459 (2012)
  38. Neang PM, Subileau M, Perrier V, Dubreucq E, J. Mol. Cat. B: Enz., 94, 36 (2013)
  39. Xie X, Tang Y, Appl. Environ. Microbiol., 73, 2054 (2007)
  40. Gao X, Xie X, Pashkov I, Sawaya MR, Laidman J, Zhang W, Cacho R, Yeates TO, Tang Y, Chem. Biol., 16, 1064 (2009)
  41. Collier S, “Commercial Biocatalytic Processes to Simvastatin and Other Molecules,” Org. Proc. Res. Dev., Barcelona, Spain, Scientific Update (2010)
  42. Dunn BJ, Khosla C, “Engineering the Acyltransferase Substrate Specificity of Assembly Line Polyketide Synthases,” J. R. Soc. Interface, 29 May 2013: 20130297.
  43. Mortison JD, Sherman DH, J. Org. Chem., 75(21), 7041 (2010)
  44. Minowa Y, Araki M, Kanehisa A, J. Mol. Biol., 368, 1500 (2007)
  45. Zhou H, Xie X, Tang Y, Curr. Opin.Biotechnol., 19, 590 (2008)
  46. Chooi YH, Tang Y, J. Org. Chem., 99339953, 77 (2012)
  47. Zabala AO, Cacho RA, Tang Y, J. Ind.Microbiol. Biotechnol., 39, 227 (2012)
  48. Truman AW, Dias MVB, Wu S, Blundell TL, Huang F, Spencer JB, Chem. Biol., 16, 676 (2009)
  49. Lee SY, Kim HU, Park JH, Park JM, Kim TY, Drug Discov. Today., 14, 78 (2009)
  50. Marienhagen J, Bott M, J. Biotechnol., 163, 166 (2013)
  51. Pickens LB, Tang Y, Chooi YT, Ann. Rev. Chem. Biomol.Eng., 2, 211 (2011)
  52. Michels PC, Khmelnitsky YL, Dordick JS, Clark DS, Trends Biotechnol., 16(5), 210 (1998)
  53. Gonzalez-Sabin J, Moran-Ramallal R, Rebolledo F, Chem. Soc. Rev., 40, 5321 (2011)
  54. Khmelnitsky YL, Budde C, Arnold JM, Usyatinsky A, Clark DS, Dordick JS, J. Am. Chem. Soc., 119(47), 11554 (1997)
  55. Loncaric C, Merriweather E, Walker KD, Chem. Biol., 13, 309 (2006)
  56. Longa RM, Lagisetti C, Coates RM, Croteaua RB, Arch. Biochem. Biophys., 477(2), 384 (2008)
  57. Nevarez DM, Mengistu YA, Nawarathne IN, Walker KD, J. Am. Chem. Soc., 131(16), 5994 (2009)
  58. Adamczyk M, Gebler JC, Mattingly PG, Tetrahedron Lett., 35, 1019 (1994)
  59. Storz T, Gu J, Wilk B, Olsen E, Tetrahededron Lett., 51, 5511 (2010)
  60. Wang P, Gao X, Chooi YH, Deng Z, Tang Y, Microbiol., 157(8), 2401 (2011)
  61. Pickens LB, Kim W, Wang P, Zhou H, Watanabe K, Gomi S, Tang Y, J. Am. Chem. Soc., 131(48), 17677 (2009)
  62. Pickens LB, Sawaya MR, Rasool H, Pashkov I, Yeates TO, Tang Y, J. Biol. Chem., 286, 41539 (2011)
  63. Wang P, Kim W, Pickens LB, Gao X, Tang Y, Angew. Chem. Int. Ed., 51, 11136 (2012)
  64. Robbel L, Marahiel MA, J. Biol. Chem., 285, 27501 (2010)
  65. Strieker M, Marahiel MA, ChemBioChem., 10, 607 (2009)
  66. Boeck LD, Fukuda DS, Abbott BJ, Debono M, J. Antibiot., 41, 1085 (1988)
  67. Debono M, Abbott BJ, Molloy RM et al., J.Antibiot., 41, 1093 (1988)
  68. Shao L, Li J, Liu A, Chang Q, Lin H, Chen D, Appl.Environ. Microb., 79(4), 1126 (2012)
  69. D’Costa VM, Mukhtar TA, Patel T, Koteva K, Waglechner N, Hughes DW, Wright GD, De Pascale G, Antimicrob. Agents Chemo., 56(2), 757 (2012)
  70. Grunewald J, Sieber SA, Mahlert C, Linne U, Marahiel MA, J. Am. Chem. Soc., 126(51), 17025 (2004)
  71. Kopp F, Grunewald J, Mahlert C, Marahiel MA, Biochem., 45, 10474 (2006)
  72. Miao V, Coeffet-Le Gal MF, Nguyen K, Brian P, Penn J, Whiting A, Steele J, Kau D, Martin S, Ford R, Gibson T, Bouchard M, Wrigley SK, Baltz RH, Chem. Biol., 13(3), 269 (2006)
  73. Nguyen KT, Ritz D, Gu JQ, et al., Proc. Natl.Acad. Sci., 103, 17462 (2006)
  74. Dubois EA, Cohen AF, Br. J. Clin.Pharmacol., 69, 2 (2010)
  75. De Mattos-Shipley K, Hayes P, Collins C, Kilaru S, Hartley A, Foster GD, Bailey AM, “Biobased Antibiotics from Basidios: a Case Study on the Identification and Manipulation of a Gene Cluster Involved in Pleuromutilin Biosynthesis from Clitopilus passeckerianus,” Proc. Of the 7th Int. Conf. Mushroom Biol. Mushroom Prod. (ICMBMP7), 224 (2011)
  76. Honda K, Kataoka M, Shimizu S, Appl. Microbiol. Biotechnol., 60(3), 288 (2002)
  77. Honda K, Sakamoto K, Kita S, Kataoka M, Shimizu S, Biosci. Biotechnol. Biochem., 67, 192 (2003)
  78. Kopp F, Marahiel MA, Nat. Prod.Rep., 24, 735 (2007)
  79. Wang M, Zhou H, Wirz M, Tang Y, Boddy CN, Biochem., 48(27), 6288 (2009)
  80. Pinto A, Wang M, Horsman M, Boddy CN, Org. Lett., 14(9), 2278 (2012)
  81. Walsh CT, ChemBioChem., 3, 125 (2002)
  82. Kiss G, Celebi-Olcum N, Moretti R, Baker D, Houk KN, Angew. Chem. Int. Ed., 52, 2 (2013)
  83. Otten L, et al., Trends Biotechnol., 28, 46 (2010)
  84. Planson AG, Carbonell P, Grigoras I, Faulon JL, Biotechnol. J., 6, 812 (2011)
  85. Pirie CM, De Mey M, Prather KLJ, Ajikumar PK, ACS Chem. Biol., 8(4), 662 (2013)