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Production of kaempferol 3-O-rhamnoside from glucose using engineered Escherichia coli

  • Short Communication
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Flavonoids are ubiquitous phenolic compounds and at least 9,000 have been isolated from plants. Most flavonoids have been isolated and assessed in terms of their biological activities. Microorganisms such as Escherichia coli and Saccharomyces cerevisiae are efficient systems for the synthesis of flavonoids. Kaempferol 3-O-rhamnoside has notable biological activities such as the inhibition of the proliferation of breast cancer cells, the absorption of glucose in the intestines, and the inhibition of the self-assembly of beta amyloids. We attempted to synthesize kaempferol 3-O-rhamnoside from glucose in E. coli. Five flavonoid biosynthetic genes [tyrosine ammonia lyase (TAL), 4-coumaroyl CoA ligase (4CL), chalcone synthase (CHS), flavonol synthase (FLS), and flavonol 3-O-rhamnosyltransferase (UGT78D1)] from tyrosine were introduced into E. coli that was engineered to increase tyrosine production. By using this approach, the production of kaempferol 3-O-rhamnoside increased to 57 mg/L.

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References

  1. Cho SY, Kim MK, Park KS, Choo H, Chong Y (2013) Quercetin-POC conjugates: differential stability and bioactivity profiles between breast cancer (MCF-7) and colorectal carcinoma (HCT116) cell lines. Bioorg Med Chem 21(7):1671–1679. doi:10.1016/j.bmc.2013.01.057

    Article  CAS  PubMed  Google Scholar 

  2. Diantini A, Subarnas A, Lestari K, Lestari K, Halimah E, Susilawati Y, Supriyatna S, Julaeha E, Achmad TH, Suradji EW, Yamazaki C, Kobayashi K, Koyama H, Abdulah R (2012) Kaempferol-3-O-rhamnoside isolated from the leaves of Schima wallichii Korth. inhibits MCF-7 breast cancer cell proliferation through activation of the caspase cascade pathway. Oncol Lett 3(5):1069–1072. doi:10.3892/ol.2012.596

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Du Y, Wei G, Linhardt RJ (2004) Total synthesis of quercetin 3-sophorotrioside. J Org Chem 69(6):2206–2209. doi:10.1021/jo035722y

    Article  CAS  PubMed  Google Scholar 

  4. Kim B-G, Joe EJ, Ahn J-H (2010) Molecular characterization of flavonol synthase from poplar and its application to the synthesis of 3-O-methylkaempferol. Biotech Lett 32(4):579–584. doi:10.1007/s10529-009-0188-x

    Article  CAS  Google Scholar 

  5. Kim BG, Kim HJ, Ahn J-H (2012) Production of bioactive flavonol rhamnosides by expression of plant genes in Escherichia coli. J Agr Food Chem 60(44):11143–11148. doi:10.1021/jf302123c

    Article  CAS  Google Scholar 

  6. Kim B-G, Lee E-R, Ahn J-H (2012) Analysis of flavonoid contents and expression of flavonoid biosynthetic genes in Populus euramericana Guinier in response to abiotic stress. J Korean Soc Appl Biol Chem 55(1):141–145. doi:10.1007/s13765-012-0025-0

    Article  CAS  Google Scholar 

  7. Kim MJ, Kim B-G, Ahn J-H (2013) Biosynthesis of bioactive O-methylated flavonoids in Escherichia coli. Appl Microbiol Biot 97(16):7195–7720. doi:10.1007/s00253-013-5020-9

    Article  CAS  Google Scholar 

  8. Lee EG, Yoon SH, Das A, Lee SH, Li C, Kim JY, Choi MS, Oh DK, Kim SW (2009) Directing vanillin production from ferulic acid by increased acetyl-CoA consumption in recombinant Escherichia coli. Biotechnol Bioeng 102(1):200–208. doi:10.1002/bit.22040

    Article  CAS  PubMed  Google Scholar 

  9. Lee Y-J, Jeon Y, Lee JS, Kim B-G, Lee CH, Ahn J-H (2007) Enzymatic synthesis of phenolic CoAs using 4-coumarate: coenzyme A ligase (4CL) from rice. Bull Korean Chem Soc 28(3):365–366

    Article  CAS  Google Scholar 

  10. Leonard E, Yan Y, Lim KH, Koffas MAG (2005) Investigation of two distinct flavone synthase for plant-specific flavone biosynthesis in Saccharomyces cerevisiae. Appl Envrion Microbiol 71(12):8241–8248. doi:10.1128/AEM.71.12.8241-8248.2005

    Article  CAS  Google Scholar 

  11. Lim E-K, Ashford DA, Bowles DJ (2006) The synthesis of small-molecule rhamnoside through the rational design of a whole-cell biocatalysis system. Chembiochem 7(8):1181–1185. doi:10.1002/cbic.200600193

    Article  CAS  PubMed  Google Scholar 

  12. Li M, Han X, Yu B (2003) Facile Synthesis of flavonoid 7-O-glycosides. J Org Chem 68(17):6842–6845. doi:10.1021/jo034553e

    Article  CAS  PubMed  Google Scholar 

  13. Lütke-Eversloh T, Stephanopoulos G (2007) l-Tyrosine production by deregulated strains of Escherichia coli. Appl Microbiol Biotechnol 75(1):103–110. doi:10.1007/s00253-006-0792-9

    Article  PubMed  Google Scholar 

  14. Lütke-Eversloh T, Stephanopoulos G (2008) Combinatorial pathway analysis for improved l-tyrosine production in Escherichia coli: identification of enzymatic bottlenecks by systematic gene overexpression. Metab Eng 10(2):69–77. doi:10.1016/j.ymben.2007.12.001

    Article  PubMed  Google Scholar 

  15. Malla S, Koffas MAG, Kazlauskas R, Kim B-G (2012) Production of 7-O-methyl aromadendrin, a medicinally valuable flavonoid, in Escherichia coli. Appl Environ Microbiol 78(3):684–694. doi:10.1128/AEM.06274-11

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Nishihara M, Nakatsuka T, Yamamura S (2005) Flavonoid components and flower color change in transgenic tobacco plants by suppression of chalcone isomerase gene. FEBS Lett 579(27):6074–6078. doi:10.1016/j.febslet.2005.09.073

    Article  CAS  PubMed  Google Scholar 

  17. Patnaik R, Liao JC (1994) Engineering of Escherichia coli central metabolism for aromatic metabolite production with near theoretical yield. Appl Environ Microbial 60(11):3903–3908

    CAS  Google Scholar 

  18. Rodrígueza P, González-Mujicaa F, Bermúdezb J, Hasegawa M (2010) Inhibition of glucose intestinal absorption by kaempferol 3-O-α-rhamnoside purified from Bauhinia megalandra leaves. Fitoterapia 81(8):1220–1223. doi:10.1016/j.fitote.2010.08.007

    Article  Google Scholar 

  19. Santos CNS, Koffas M, Stephanopoulos (2011) Optimization of a heterologous pathway for the production of flavonoids from glucose. Met Eng 13(4):392–400. doi:10.1016/j.ymben.2011.02.002

    Article  CAS  Google Scholar 

  20. Sharoar MG, Thapa A, Shahnawaz M, Ramasamy VS, Woo E-R, Shin SY, Park I-S (2012) Kaempferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates. J Biomed Sci 19:104. doi:10.1186/1423-0127-19-104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Tahara S (2007) A journey of twenty-five years through the ecological biochemistry of flavonoids. Biosci Biotechnol Biochem 71(6):1387–1404. doi:10.1271/bbb.70028

    Article  CAS  PubMed  Google Scholar 

  22. Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N (2007) Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: chemical diversity, impact on plant biology and human health. Biotech J 2(10):1214–1234. doi:10.1002/biot.200700184

    Article  CAS  Google Scholar 

  23. Watts KT, Lee PC, Schmidt-Dannert C (2004) Exploring recombinant flavonoid biosynthesis in metabolically engineered Escherichia coli. Chembiochem 5(4):500–507. doi:10.1002/cbic.200300783

    Article  CAS  PubMed  Google Scholar 

  24. Winkel-Shirley B (2001) Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology. Plant Physiol 126(2):485–493. doi:10.1104/pp.126.2.485

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Yan Y, Kohli A, Koffas MAG (2005) Biosynthesis of natural flavones in Saccharomyces cerevisiae. Appl Envrion Microbiol 71(9):5610–5613. doi:10.1128/aem.71.12.8241-8248.2005

    Article  CAS  Google Scholar 

  26. Yi J, Li K, Draths KM, Frost JW (2002) Modulation of phosphoenolpyruvate synthase expression increases shikimate pathway product yields in E. coli. Biotechnol Prog 18(6):1141–1148. doi:10.1021/bp020101w

    Article  CAS  PubMed  Google Scholar 

  27. Yonekura-Sakakibara K, Tohge T, Niida R, Saito K (2007) Identification of a flavonol 7-O-rhamnosyltransferase gene determining flavonoid pattern in Arabidopsis by transcriptome coexpression analysis and reverse genetics. J Biol Chem 282(20):14932–14941. doi:10.1074/jbc.M611498200

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant from the Next-Generation BioGreen 21 Program (PJ00948301), Rural Development Administration, Republic of Korea, and by the Priority Research Centers Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2009-0093824).

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Authors and Affiliations

  1. Department of Forest Resources, Gyeongnam National University of Science and Technology, 33 Dongjin-ro, Gyeongsangman-do, Jinju, 660-758, Korea

    Bong-Gyu Kim

  2. Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143-701, Korea

    So-Mi Yang, So Hyun Han & Joong-Hoon Ahn

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  1. So-Mi Yang
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  2. So Hyun Han
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Correspondence to Joong-Hoon Ahn.

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Yang, SM., Han, S.H., Kim, BG. et al. Production of kaempferol 3-O-rhamnoside from glucose using engineered Escherichia coli . J Ind Microbiol Biotechnol 41, 1311–1318 (2014). https://doi.org/10.1007/s10295-014-1465-9

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  • DOI: https://doi.org/10.1007/s10295-014-1465-9

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