Molecules and Cells

  • 제38권4호
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  • Pages.318-326
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  • 2015
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Metabolic Engineering for Resveratrol Derivative Biosynthesis in Escherichia coli

  • Jeong, Yu Jeong (Eco-friendly Bio-Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Woo, Su Gyeong (Eco-friendly Bio-Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • An, Chul Han (Eco-friendly Bio-Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jeong, Hyung Jae (Eco-friendly Bio-Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Hong, Young-Soo (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Young-Min (Department of Food Science and Technology and Functional Food Research Center, Chonnam National University) ;
  • Ryu, Young Bae (Eco-friendly Bio-Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Rho, Mun-Chual (Eco-friendly Bio-Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Woo Song (Eco-friendly Bio-Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Cha Young (Eco-friendly Bio-Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • 투고 : 2014.07.01
  • 심사 : 2014.12.15
  • 발행 : 2015.04.30
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초록

We previously reported that the SbROMT3syn recombinant protein catalyzes the production of the methylated resveratrol derivatives pinostilbene and pterostilbene by methylating substrate resveratrol in recombinant E. coli. To further study the production of stilbene compounds in E. coli by the expression of enzymes involved in stilbene biosynthesis, we isolated three stilbene synthase (STS) genes from rhubarb, peanut, and grape as well as two resveratrol O-methyltransferase (ROMT) genes from grape and sorghum. The ability of RpSTS to produce resveratrol in recombinant E. coli was compared with other AhSTS and VrSTS genes. Out of three STS, only AhSTS was able to produce resveratrol from p-coumaric acid. Thus, to improve the solubility of RpSTS, VrROMT, and SbROMT3 in E. coli, we synthesized the RpSTS, VrROMT and SbROMT3 genes following codon-optimization and expressed one or both genes together with the cinnamate/4-coumarate:coenzyme A ligase (CCL) gene from Streptomyces coelicolor. Our HPLC and LC-MS analyses showed that recombinant E. coli expressing both ScCCL and RpSTSsyn led to the production of resveratrol when p-coumaric acid was used as the precursor. In addition, incorporation of SbROMT3syn in recombinant E. coli cells produced resveratrol and its mono-methylated derivative, pinostilbene, as the major products from p-coumaric acid. However, very small amounts of pterostilbene were only detectable in the recombinant E. coli cells expressing the ScCCL, RpSTSsyn and SbROMT3syn genes. These results suggest that RpSTSsyn exhibits an enhanced enzyme activity to produce resveratrol and SbROMT3syn catalyzes the methylation of resveratrol to produce pinostilbene in E. coli cells.

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참고문헌

  1. Baur, J.A., Pearson, K.J., Price, N.L., Jamieson, H.A., Lerin, C., Kalra, A., Prabhu, V.V., Allard, J.S., Lopez-Lluch, G., Lewis, K., et al. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444, 337-342. https://doi.org/10.1038/nature05354
  2. Becker, J.V., Armstrong, G.O., van der Merwe, M.J., Lambrechts, M.G., Vivier, M.A., and Pretorius, I.S. (2003). Metabolic engineering of Saccharomyces cerevisiae for the synthesis of the wine-related antioxidant resveratrol. FEMS Yeast Res. 4, 79-85. https://doi.org/10.1016/S1567-1356(03)00157-0
  3. Beekwilder, J., Wolswinkel, R., Jonker, H., Hall, R., de Vos, C.H., and Bovy, A. (2006). Production of resveratrol in recombinant microorganisms. Appl. Environ. Microbiol. 72, 5670-5672. https://doi.org/10.1128/AEM.00609-06
  4. Choi, O., Wu, C.Z., Kang, S.Y., Ahn, J.S., Uhm, T.B., and Hong, Y.S. (2011). Biosynthesis of plant-specific phenylpropanoids by construction of an artificial biosynthetic pathway in Escherichia coli. J. Ind. Microbiol. Biotechnol. 38, 1657-1665. https://doi.org/10.1007/s10295-011-0954-3
  5. Delaunois, B., Cordelier, S., Conreux, A., Clement, C., and Jeandet, P. (2009). Molecular engineering of resveratrol in plants. Plant Biotechnol. J. 7, 2-12. https://doi.org/10.1111/j.1467-7652.2008.00377.x
  6. Foust, C.M. (1992). Rhubarb: The wondrous drug. (Princeton, NJ, USA: Princeton University Press).
  7. Fremont, L. (2000). Biological effects of resveratrol. Life Sci. 66, 663-673. https://doi.org/10.1016/S0024-3205(99)00410-5
  8. Horinouchi, S. (2009). Combinatorial biosynthesis of plant medicinal polyketides by microorganisms. Curr. Opin. Chem. Biol. 13, 197-204. https://doi.org/10.1016/j.cbpa.2009.02.004
  9. Jeong, Y.J., An, C.H., Woo, S.G., Jeong, H.J., Kim, Y.-M., Park, S.-J., Yoon, B.D., and Kim, C.Y. (2014). Production of pinostilbene compounds by the expression of resveratrol O-methyltransferase genes in Escherichia coli. Enzyme Microb. Tech. 54, 8-14. https://doi.org/10.1016/j.enzmictec.2013.09.005
  10. Kaneko, M., Ohnishi, Y., and Horinouchi, S. (2003). Cinnamate: coenzyme A ligase from the filamentous bacterium Streptomyces coelicolor A3(2). J. Bacteriol. 185, 20-27. https://doi.org/10.1128/JB.185.1.20-27.2003
  11. Kashiwada, Y., Nonaka, G., Nishioka, I., Nishizawa, M., and Yamagishi, T. (1988). Studies on rhubarb (Rhein Rhizoma). XIV. Isolation and characterization of stilbene glucosides from Chinese rhubarb. Chem. Pharm. Bull. 36, 1545-1549. https://doi.org/10.1248/cpb.36.1545
  12. Katsuyama, Y., Funa, N., Miyahisa, I., and Horinouchi, S. (2007). Synthesis of unnatural flavonoids and stilbenes by exploiting the plant biosynthetic pathway in Escherichia coli. Chem. Biol. 14, 613-621. https://doi.org/10.1016/j.chembiol.2007.05.004
  13. Lee, S.K., Nam, K.A., Hoe, Y.H., Min, H.Y., Kim, E.Y., Ko, H., Song, S., Lee, T., and Kim, S. (2003). Synthesis and evaluation of cytotoxicity of stilbene analogues. Arch. Pharm. Res. 26, 253-257. https://doi.org/10.1007/BF02976951
  14. Lee, S.W., Hwang, B.S., Kim, M.H., Park, C.S., Lee, W.S., Oh, H.M., and Rho, M.C. (2012). Inhibition of LFA-1/ICAM-1- mediated cell adhesion by stilbene derivatives from Rheum undulatum. Arch. Pharm. Res. 35, 1763-1770. https://doi.org/10.1007/s12272-012-1008-8
  15. Melchior, F., and Kindl, H. (1990). Grapevine stilbene synthase cDNA only slightly differing from chalcone synthase cDNA is expressed in Escherichia coli into a catalytically active enzyme. FEBS Lett. 268, 17-20. https://doi.org/10.1016/0014-5793(90)80961-H
  16. Remsberg, C.M., Yanez, J.A., Ohgami, Y., Vega-Villa, K.R., Rimando, A.M., and Davies, N.M. (2008). Pharmacometrics of pterostilbene: preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity. Phytother. Res. 22, 169-179. https://doi.org/10.1002/ptr.2277
  17. Rimando, A.M., Pan, Z., Polashock, J.J., Dayan, F.E., Mizuno, C.S., Snook, M.E., Liu, C.J., and Baerson, S.R. (2012). In planta production of the highly potent resveratrol analogue pterostilbene via stilbene synthase and O-methyltransferase co-expression. Plant Biotechnol. J. 10, 269-283. https://doi.org/10.1111/j.1467-7652.2011.00657.x
  18. Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual. (2nd ed). Vol. 1, 2, 3. (NY, USA: Cold Spring Harbor Laboratory Press).
  19. Schmidlin, L., Poutaraud, A., Claudel, P., Mestre, P., Prado, E., Santos-Rosa, M., Wiedemann-Merdinoglu, S., Karst, F., Merdinoglu, D., and Hugueney, P. (2008). A stress-inducible resveratrol O-methyltransferase involved in the biosynthesis of pterostilbene in grapevine. Plant Physiol. 148, 1630-1639. https://doi.org/10.1104/pp.108.126003
  20. Sparvoli, F., Martin, C., Scienza, A., Gavazzi, G., and Tonelli, C. (1994). Cloning and molecular analysis of structural genes involved in flavonoid and stilbene biosynthesis in grape (Vitis vinifera L.). Plant Mol. Biol. 24, 743-755. https://doi.org/10.1007/BF00029856
  21. Ulrich, S., Wolter, F., and Stein, J.M. (2005). Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in carcinogenesis. Mol. Nutr. Food. Res. 49, 452-461. https://doi.org/10.1002/mnfr.200400081
  22. Ververidis, F., Trantas, E., Douglas, C., Vollmer, G., Kretzschmar, G., and Panopoulos, N. (2007). Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part II: Reconstruction of multienzyme pathways in plants and microbes. Biotechnol. J. 2, 1235-1249. https://doi.org/10.1002/biot.200700184
  23. Walle, T., Hsieh, F., DeLegge, M.H., Oatis, J.E. Jr, and Walle, U.K. (2004). High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Dispos. 32, 1377-1382. https://doi.org/10.1124/dmd.104.000885
  24. Wang, T.T., Schoene, N.W., Kim, Y.S., Mizuno, C.S., and Rimando, A.M. (2010). Differential effects of resveratrol and its naturally occurring methylether analogs on cell cycle and apoptosis in human androgen-responsive LNCaP cancer cells. Mol. Nutr. Food Res. 54, 335-344. https://doi.org/10.1002/mnfr.200900143
  25. Watts, K.T., Lee, P.C., and Schmidt-Dannert, C. (2006). Biosynthesis of plant-specific stilbene polyketides in metabolically engineered Escherichia coli. BMC Biotechnol. 6, 22. https://doi.org/10.1186/1472-6750-6-22
  26. Zhang, Y., Li, S.Z., Li, J., Pan, X., Cahoon, R.E., Jaworski, J.G., Wang, X., Jez, J.M., Chen, F., and Yu, O. (2006). Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and Mammalian cells. J. Am. Chem. Soc. 128, 13030-13031 https://doi.org/10.1021/ja0622094

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  6. De novobiosynthesis of resveratrol by site-specific integration of heterologous genes inEscherichia coli vol.363, pp.8, 2016, https://doi.org/10.1093/femsle/fnw061
  7. Secondary metabolism of pharmaceuticals in the plant in vitro cultures: strategies, approaches, and limitations to achieving higher yield vol.132, pp.2, 2018, https://doi.org/10.1007/s11240-017-1332-2
  8. Expanding the Chemical Palette of Industrial Microbes: Metabolic Engineering for Type III PKS-Derived Polyketides pp.18606768, 2018, https://doi.org/10.1002/biot.201700463
  9. Resveratrol and Related Stilbenoids, Nutraceutical/Dietary Complements with Health-Promoting Actions: Industrial Production, Safety, and the Search for Mode of Action vol.17, pp.4, 2018, https://doi.org/10.1111/1541-4337.12359
  10. An innovative biotransformation to produce resveratrol by Bacillus safensis vol.9, pp.27, 2015, https://doi.org/10.1039/c9ra01338e
  11. Biotechnological Advances in Resveratrol Production and its Chemical Diversity vol.24, pp.14, 2015, https://doi.org/10.3390/molecules24142571