한국미생물·생명공학회지 (Microbiology and Biotechnology Letters)

  • 제50권2호
  • /
  • Pages.218-227
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  • 2022
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  • 1598-642X(pISSN)
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  • 2234-7305(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
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Synthesis of α-cichoriin Using Deinococcus geothermalis Amylosucrase and Its Antiproliferative Effect

  • Moon, Keumok (Microbiological Resource Research Institute, Pusan National University) ;
  • Park, Hyun Su (Manufacturing Divisional Group, Celltrion, Inc.) ;
  • Lee, Areum (Department of Microbiology, Pusan National University) ;
  • Min, Jugyeong (Department of Microbiology, Pusan National University) ;
  • Park, Yunjung (Department of Microbiology, Pusan National University) ;
  • Cha, Jaeho (Microbiological Resource Research Institute, Pusan National University)
  • 투고 : 2022.03.10
  • 심사 : 2022.04.14
  • 발행 : 2022.06.28
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초록

Glycosylation of aesculetin was performed using amylosucrase from the hyperthermophilic bacterium Deinococcus geothermalis DSM 11300 to improve the solubility and biological activity of aesculetin. A newly synthesized aesculetin glycoside was identified as α-cichoriin (aesculetin 7-α-D-glucoside) by nuclear magnetic resonance analysis. The solubility of α-cichoriin was 11 times higher than that of aesculetin because of the attached glucose moiety. Aesculetin and α-cichoriin had no significant effect on the proliferation of normal cells, such as RAW 264.7, but they showed a cell proliferation inhibitory effect on B16F10 melanoma cells. Unlike treatment with aesculetin and α-cichoriin, aesculin (aesculetin 6-β-D-glucoside) showed no antiproliferative activity in B16F10 cells. Based on the molecular structures of aesculin and α-cichoriin, the position where glucose binds to aesculetin and the anomeric configuration between glucose and aesculetin are thought to be important for exerting an antiproliferative effect on the B16F10 cell line. Based on these results, we propose that α-cichoriin, the α-glycosylated form of aesculetin, may serve as a model for developing phytochemical analogs with therapeutic potential for the treatment of diseases associated with tumor cell proliferation without cytotoxicity to normal cells.

키워드

과제정보

This work was supported by a 2-Year Research grant from the Pusan National University.

참고문헌

  1. Liang C, Ju W, Pei S, Tang Y, Xiao Y. 2017. Pharmacological activities and synthesis of esculetin and its derivatives: A minireview. Molecules 22: 387. https://doi.org/10.3390/molecules22030387
  2. Kaneko T, Tahara S, Takabayashi F. 2007. Inhibitory effect of natural coumarin compounds, esculetin and esculin, on oxidative DNA damage and formation of aberrant crypt foci and tumors induced by 1,2-dimethylhydrazine in rat colons. Biol. Pharm. Bull. 30: 2052-2057. https://doi.org/10.1248/bpb.30.2052
  3. Marinova EM, Yanishlieva NV, Kostova IN. 1994. Antioxidative action of the ethanolic extract and some hydroxycoumarins of Fraxinus ornus bark. Food Chem. 51: 125-132. https://doi.org/10.1016/0308-8146(94)90245-3
  4. Fylakatakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN. 2004. Natural and synthetic coumarin derivatives with anti-inflammatory/antioxidant activities. Curr. Pharm. Des. 10: 3813-3833. https://doi.org/10.2174/1381612043382710
  5. Riveiro ME, DeKimpe N, Moglioni A, Vazquez R, Monczor F, Shayo C, et al. 2010. Coumarins: old compounds with novel, promising therapeutic perspectives. Curr. Med. Chem. 17: 1325-1338. https://doi.org/10.2174/092986710790936284
  6. Chu CY, Tsai YY, Wang CJ, Lin WL, Tseng TH. 2001. Induction of apoptosis by esculetin in human leukemia cells. Eur. J. Pharmacol. 416: 25-32. https://doi.org/10.1016/S0014-2999(01)00859-7
  7. Pan L, Huang YW, Guh JH, Chang YL, Peng CY, Teng CM. 2003. Esculetin inhibits Ras-mediated cell proliferation and attenuates vascular restenosis following angioplasty in rats. Biochem. Pharmacol. 65: 1897-1905. https://doi.org/10.1016/S0006-2952(03)00161-8
  8. Finn GJ, Kenealy E, Creaven BS, Egan DA. 2002. In vitro cytotoxic potential and mechanism of action of selected coumarins, using human renal cell lines. Cancer Lett. 183: 61-68. https://doi.org/10.1016/S0304-3835(02)00102-7
  9. Kawaii S, Tomono Y, Ogawa K, Sugiura M, Yano M, Yoshizawa Y. 2001. The antiproliferative effect of coumarins on several cancer cell lines. Anticancer Res. 21: 917-924.
  10. Kawase M, Sakagami H, Hashimoto K, Tani S, Hauer H, Chatterjee SS. 2003. Structure-cytotoxic activity relationships of simple hydroxylated coumarins. Anticancer Res. 23: 3243-3246.
  11. Lacy A, O'Kennedy R. 2004. Studies on coumarins and coumarin-related compounds to determine their therapeutic role in the treatment of cancer. Curr. Pharm. Des. 10: 3797-3811. https://doi.org/10.2174/1381612043382693
  12. Al-Akhras MAH, Aljarrah K, Al-Khateeb H, Jaradat A, Al-Omari A, Al-Nasser A, et al. 2012. Introducing Cichorium Pumilum as a potential therapeutical agent against drug-induced benign breast tumor in rats. Electromagn. Biol. Med. 31: 299-309. https://doi.org/10.3109/15368378.2012.662193
  13. Park S, Moon K, Park CS, Jung DH, Cha J. 2018. Synthesis of aesculetin and aesculin glycosides using engineered Escherichia coli expressing Neisseria polysaccharea amylosucrase. J. Microbiol. Biotechnol. 28: 566-570. https://doi.org/10.4014/jmb.1711.11055
  14. Liang SC, Ge GB, Liu HX, Zhang YY, Wang LM, Zhang JW, et al. 2010. Identification and characterization of human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of daphnetin. Drug Metab. Dispos. 38: 973-980. https://doi.org/10.1124/dmd.109.030734
  15. Xia YL, Liang SC, Zhu LL, Ge GB, He GY, Ning J, et al. 2014. Identification and characterization of human UDP-glucuronosyltransferases responsible for the glucuronidation of fraxetin. Drug Metab. Pharmacokinet. 29: 135-140. https://doi.org/10.2133/dmpk.DMPK-13-RG-059
  16. Zhang SF, Ma JH, Chen SR, Li HY, Xin JF. 2007. Improved synthesis technics of 6,7-dimethoxy coumarin. J. Hebei Univ. Sci. Technol. 28: 24-25. https://doi.org/10.3969/j.issn.1008-1542.2007.01.007
  17. Bull JA, Lujan C, Hutchings MG, Peter Q. 2009. Application of the BHQ benzannulation reaction to the synthesis of benzo-fused coumarins. Tetrahedron Lett. 50: 3617-3620. https://doi.org/10.1016/j.tetlet.2009.03.077
  18. Nemoto T, Ohshima T, Shibasaki M. 2003. Enantioselective total syntheses of (+)-decursin and related natural compounds using catalytic asymmetric epoxidation of an enon. Tetrahedron 59: 6889-6897. https://doi.org/10.1016/S0040-4020(03)00861-5
  19. Lim EK. 2005. Plant glycosyltransferases: their potential as novel biocatalysts. Chem. Eur. J. 11: 5486-5494. https://doi.org/10.1002/chem.200500115
  20. Durr C, Hoffmeister D, Wohlert SE, Ichinose K, Weber M, von Mulert U, et al. 2004. The glycosyltransferase UrdGT2 catalyzes both C-and O-glycosidic sugar transfers. Angew. Chem. Int. Ed. 43: 2962-2965. https://doi.org/10.1002/anie.200453758
  21. Hao B, Caulfield JC, Hamilton ML, Pickett JA, Midega CAO, Khan ZR, et al. 2016. Biosynthesis of natural and novel C-glycosylflavones utilizing recombinant Oryza sativa C-glycosyltransferase (OsCGT) and Desmodium incanum root proteins. Phytochemistry 125: 73-87. https://doi.org/10.1016/j.phytochem.2016.02.013
  22. Wang X, Li C, Zhou C, Li J, Zhang Y. 2017. Molecular characterization of the C-glucosylation for puerarin biosynthesis in Pueraria lobata. Plant J. 90: 535-546. https://doi.org/10.1111/tpj.13510
  23. Ito T, Fujimoto S, Suito F, Shimosaka M, Taguchi G. 2017. C-Glycosyltransferases catalyzing the formation of di-C-glucosyl flavonoids in citrus plants. Plant J. 91: 187-198. https://doi.org/10.1111/tpj.13555
  24. Chen D, Chen R, Wang R, Li J, Xie K, Bian C, et al. 2015. Probing the catalytic promiscuity of a regio- and stereospecific C-glycosyltransferase from Mangifera indica. J. Angew. Chem. Int. Ed. 54: 12678-12682. https://doi.org/10.1002/anie.201506505
  25. Chen D, Sun L, Chen R, Xie K, Yang L, Dai J. 2016. Enzymatic synthesis of acylphloroglucinol 3-C-glucosides from 2-O-glucosides using a C-glycosyltransferase from Mangifera indica. Chem. Eur. J. 22: 5873-5877. https://doi.org/10.1002/chem.201600411
  26. Hoffmeister D, Drager G, Ichinose K, Rohr J, Bechthold A. 2003. The C-glycosyltransferase UrdGT2 is unselective toward ᴰ- and ᴸ-configured nucleotide-bound rhodinoses. J. Am. Chem. Soc. 125: 4678-4679. https://doi.org/10.1021/ja029645k
  27. Andersen-Ranberg J, Kongstad KT, Nafisi M, Staerk D, Okkels FT, Mortensen UH, et al. 2017. Synthesis of C-glucosylated octaketide anthraquinones in Nicotiana benthamiana by using a multispecies-based biosynthetic pathway. ChemBioChem 18: 1893-1897. https://doi.org/10.1002/cbic.201700331
  28. Salem SM, Weidenbach S, Rohr J. 2017. Two cooperative glycosyltransferases are responsible for the sugar diversity of saquayamycins isolated from Streptomyces sp. KY 40-1. ACS Chem. Biol. 12: 2529-2534. https://doi.org/10.1021/acschembio.7b00453
  29. Seo DH, Yoo SH, Choi SJ, Kim YR, Park CS. 2020. Versatile biotechnological applications of amylosucrase, a novel glucosyltransferase. Food Sci. Biotechnol. 29: 1-16. https://doi.org/10.1007/s10068-019-00686-6
  30. Chiang C-M, Wang T-Y, Wu J-Y, Zhang Y-R, Lin S-Y, Chang T-S. 2021. Production of new isoflavone diglucosides from glycosylation of 8-hydroxydaidzein by Deinococcus geothermalis amylosucrase. Fermentation 7: 232. https://doi.org/10.3390/fermentation7040232
  31. Rha CS, Kim HG, Baek NI, Kim, DO, Park CS. 2020. Using amylosucrase for the controlled synthesis of novel isoquercitrin glycosides with different glycosidic linkages. J. Agric. Food Chem. 68: 13798-13805. https://doi.org/10.1021/acs.jafc.0c05625
  32. Rha CS, Kim ER, Kim YJ, Jung YS, Kim DO, Park CS. 2019. Simple and efficient production of highly soluble daidzin glycosides by amylosucrase from Deinococcus geothermalis. J. Agric. Food Chem. 67: 12824-12832. https://doi.org/10.1021/acs.jafc.9b05380
  33. Cho HK, Kim HH, Seo DH, Jung JH, Park JH, Baek NI, et al. 2011. Biosynthesis of (+)-catechin glycosides using recombinant amylosucrase from Deinococcus geothermalis DSM 11300. Enzyme Microb. Technol. 49: 246-253. https://doi.org/10.1016/j.enzmictec.2011.05.007
  34. Moon YH, Lee JH, Ahn JS, Nam SH, Oh DK, Park DH, et al. 2006. Synthesis, structure analyses, and characterization of novel epigallocatechin gallate (EGCG) glycosides using the glucansucrase from Leuconostoc mesenteroides B-1299CB. J. Agric. Food Chem. 54: 1230-1237. https://doi.org/10.1021/jf052359i
  35. Lee SJ, Kim JC, Kim MJ, Kitaoka M, Park CS, Lee SY, et al. 1999. Transglycosylation of naringin by Bacillus stearothermophilus maltogenic amylase to give glycosylated naringin. J. Agric. Food Chem. 47: 3669-3674. https://doi.org/10.1021/jf990034u
  36. Ko JA, Ryu YB, Park T, Jeong HJ, Kim JH, Park SJ, et al. 2012. Enzymatic synthesis of puerarin glucosides using Leuconostoc dextransucrase. J. Microbiol. Biotechnol. 22: 1224-1229. https://doi.org/10.4014/jmb.1202.02007
  37. Moon YH, Lee JH, Jhon DY, Jun WJ, Kang SS, Sim J, et al. 2007. Synthesis and characterization of novel quercetin-α-ᴰ-glucopyranosides using glucansucrase from Leuconostoc mesenteroides. Enzyme Microb. Technol. 40: 1124-1129. https://doi.org/10.1016/j.enzmictec.2006.08.019
  38. Acero JL, Benitez JF, Real FJ, Leal AI, Sordo A. 2005. Oxidation of esculetin, a model pollutant present in cork processing wastewaters, by chemical methods. Ozone: Sci. Eng. 27: 317-326. https://doi.org/10.1080/01919510591008344
  39. Hollman PC, Bijsman MN, van Gameren Y, Cnossen EP, de Vries JH, Katan MB. 1999. The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic. Res. 32: 569-573.
  40. Jiang JR, Yuan S, Ding JF, Zhu SC, Xu HD, Chen T, et al. 2008. Conversion of puerarin into its 7-O-glycoside derivatives by Micro-bacterium oxydans (CGMCC 1788) to improve its water solubility and pharmacokinetic properties. Appl. Microbiol. Biotechnol. 81: 647-657. https://doi.org/10.1007/s00253-008-1683-z
  41. Yamada M, Tanabe F, Arai N, Mitsuzumi H, Miwa Y, Kubota M, et al. 2006. Bioavailability of glucosyl hesperidin in rats. Biosci. Biotechnol. Biochem. 70: 1386-1394. https://doi.org/10.1271/bbb.50657
  42. Marshall ME, Butler K, Fried A. 1991. Phase I evaluation of coumarin (1,2-benzopyrone) and cimetidine in patients with advanced malignancies. Mol. Biother. 3: 170-178.
  43. Mohler JL, Gomella LG, Crawford ED, Glode LM, Zippe CD, Fair WR, et al. 1992. Phase II evaluation of coumarin (1,2-benzopyrone) in metastatic prostatic carcinoma. Prostate 20: 123-131. https://doi.org/10.1002/pros.2990200208
  44. Thornes RD, Daly L, Lynch G, Breslin B, Browne H, Browne GY, et al. 1994. Treatment with coumarin to prevent or delay recurrence of malignant melanoma. J. Cancer Res. Clin. Oncol. 120: 32-34.
  45. Egan D, O'Kennedy R, Moran E, Cox D, Prosser E, Thornes RD. 1990. The pharmacology, metabolism, analysis, and applications of coumarin and coumarin-related compounds. Drug Metab. Res. 22: 503-529. https://doi.org/10.3109/03602539008991449
  46. Funayama M, Arakawa H, Yamamoto R, Nishino T, Shin T, Murao S. 1995. Effects of α- and β-Arbutin on activity of tyrosinases from mushroom and mouse melanoma. Biosci. Biotech. Biochem. 59: 143-144. https://doi.org/10.1271/bbb.59.143