Advertisement

Microbial Modifications of Flavonols

  • Prakash Parajuli
  • Biplav Shrestha
  • Jae Kyung Sohng
  • Ramesh Prasad Pandey
Chapter
Part of the Environmental Chemistry for a Sustainable World book series (ECSW, volume 26)

Abstract

Development of microbial cell factories via application of synthetic biology, protein engineering for metabolic engineering has revolutionized the maximum use of microbial consortium for biosynthesis and structural alteration of valuable flavonoids. From a single enzyme expression to complex metabolic pathway, it has been possible to manipulate strains of Escherichia coli, Saccharomyces cerevisiae, Streptomyces, and Bacillus for target-based modification of compounds to industrial level in laboratory. Biotransformation, a biotechnological approach, can be applied to structurally modify and generate library of natural products such as flavonoid derivatives.

This chapter highlights the significance of engineered new molecules and biotransformation approaches used to generate flavonoids by the use of microbial platforms. Basically, E. coli has been engineered by expressing secondary metabolites post modifying enzymes, glycosyltransferases, O-methyl transferases, and prenyltransferases, in particular to generate the natural and nonnatural flavonol derivatives. Indigenously present cytoplasmic cofactors, coenzymes, and donor substrates are utilized by such enzymes for target-based chemical modifications. Engineering the central carbon flux pathway to enhance the flow of carbon toward target donor substrates and cofactors such as nucleotide diphosphate (NDP)-sugars, S-adenosyl methionine, dimethylallyl pyrophosphate, and other cofactors which enhanced the cytoplasmic pool while maximizing the biotransformation efficiency for level up production are discussed. Moreover, heterologous expression of different pathway genes from different organisms and engineering of glycosyltransferases and O-methyl transferases into bacterial host does help to generate nonnatural flavonol glycosides.

Keywords

Flavonoid Flavonol Microbial engineering Biotransformation Quercetin 3-O-glucoside Glycosyltransferase Methyltransferase Polyphenols Nutraceuticals 

Notes

Acknowledgments

This research was supported by grant from National Research Foundation of Korea to Ramesh Prasad Pandey (Grant no. 2017R1C1B5018056).

References

  1. Ahmad A, Ali T, Park HY, Badshah H, Rehman SU, Kim MO (2017) Neuroprotective effect of fisetin against amyloid-beta-induced cognitive/synaptic dysfunction, neuroinflammation, and neurodegeneration in adult mice. Mol Neurobiol 54:2269–2285.  https://doi.org/10.1007/s12035-016-9795-4 CrossRefGoogle Scholar
  2. Borsari C, Luciani R, Pozzi C, Poehner I, Henrich S, Trande M, al e (2016) Profiling of flavonoid derivatives for the development of anti-trypanosomatidic drugs. J Med Chem 59:7598–7616.  https://doi.org/10.1021/acs.jmedchem.6b00698 CrossRefGoogle Scholar
  3. Buchter C, Ackermann D, Honnen S, Amold N, Havermann S, Koch K, Watjen W (2015) Methylated derivatives of myricetin enhance life span in Caenorhabditis elegans dependent on the transcription factor DAF-16. Food Funct 6:3383–3392.  https://doi.org/10.1039/c5fo00463b CrossRefGoogle Scholar
  4. Cassani J, Dorantes-Barron AM, Novales LM, Real GA, Estrada_reyes R (2014) Anti-depressant-like effect of kaempferitrin isolated from Justicia spicigera Schltdl (Acanthaceae) in two behavior models in mice: evidence for the involvement of the serotonergic system. Molecules 19:21442–21462.  https://doi.org/10.3390/molecules191221442 CrossRefGoogle Scholar
  5. Chiang CM, Ding HY, Tsai YT, Chang TS (2015) Production of two novel methoxy-isoflavones from biotransformation of 8-hydroxydaidzein by recombinant Escherichia coli expressing O-methyltransferase SpOMT2884 from Streptomyces peucetius. Int J Mol Sci 16:27816–27823.  https://doi.org/10.3390/ijms161126070 CrossRefGoogle Scholar
  6. Choi HJ, Kim JH, Lee CH, Ahn YJ, Song JH, Baek SH, Kwon DH (2009) Antiviral activity of quercetin 7-O-rhamnoside against porcine epidemic diarrhea virus. Antivir Res 81:77–81.  https://doi.org/10.1016/j.antiviral.2008.10.002 CrossRefGoogle Scholar
  7. Currais A, Prior M, Dargusch R, Armando A, Ehren J, Schubert D, Quehenberger O, Maher P (2014) Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer’s disease transgenic mice. Aging Cell 13:379–390.  https://doi.org/10.1111/acel.12185 CrossRefGoogle Scholar
  8. Da Silva D, Casanova LM, Marcondes MC, Espindola-Netto JM, Paixão LP, De Melo GO, Zancan P, Sola-Penna M, Costa SS (2014) Antidiabetic activity of Sedum dendroideum: metabolic enzymes as putative targets for the bioactive flavonoid kaempferitrin. IUBMB Life 66:361–370.  https://doi.org/10.1002/iub.1270 CrossRefGoogle Scholar
  9. Darsandhari S, Dhakal D, Shrestha B, Parajuli P, Seo JH, Kim TS, Sohng JK (2018) Characterization of regioselective flavonoid O-methyltransferase from the Streptomyces Sp. KCTC 0041BP. Enzym Microb Technol 113:29–36.  https://doi.org/10.1016/j.enzmictec.2018.02.007 CrossRefGoogle Scholar
  10. De Bruyn F, Van Brempt M, Maertens J, Van Bellegem W, Duchi D, De Mey M (2015) Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides. Microb Cell Factories 14:138.  https://doi.org/10.1186/s12934-015-0326-1 CrossRefGoogle Scholar
  11. Dos Santos AE, Kuster RM, Yamamoto KA, Salles TS, Campos R, de Meneses MD, Soares MR, Ferreira D (2014) Quercetin and quercetin 3-O-glycosides from bauhinia longifolia (Bong.) steud. Show anti-mayaro virus activity. Parasit Vectors 7:130.  https://doi.org/10.1186/1756-3305-7-130 CrossRefGoogle Scholar
  12. Gaudry A, Bos S, Viranaicken W, Roche M, Krejbich-Trotot P, Gadea G, Despres P, EI-Kalamouni C (2018) The flavonoid isoquercitrin precludes initiation of Zika virus infection in human cells. Int J Mol Sci pii:E1093.  https://doi.org/10.3390/ijms19041093 CrossRefGoogle Scholar
  13. Gong EJ, Park HR, Kim ME, Piao S, Lee E, Jo DG, Chung HY, Ha NC, Mattson MP, Lee J (2011) Morin attenuates tau hyperphosphorylation by inhibiting GSK3β. Neurobiol Dis 44:223–230.  https://doi.org/10.1016/j.nbd.2011.07.005 CrossRefGoogle Scholar
  14. Gopi K, Anbarasu K, Renu K, Jayanthi S, Vishwanath BS, Jayaraman G (2016) Quercetin 3-O-rhamnoside from Euphorbia hirta protects against snake Venom induced toxicity. Biochim Biophys Acta 1860:1528–1540.  https://doi.org/10.1016/j.bbagen.2016.03.031 CrossRefGoogle Scholar
  15. Han SH, Kim BG, Yoon JA, Chong Y, Ahn JH (2014) Synthesis of flavonoid O-pentosides by Escherichia coli through engineering of nucleotide sugar pathways and glycosyltransferase. Appl Environ Microbiol 80:2754–2762.  https://doi.org/10.1128/AEM.03797-13 CrossRefGoogle Scholar
  16. Hosny M, Dhar K, Rosazza JP (2001) Hydroxylations and methylations of quercetin, fisetin, and catechin by Streptomyces griseus. J Nat Prod 64:462–465.  https://doi.org/10.1021/np000457m CrossRefGoogle Scholar
  17. Itoh N, Iwata C, Toda H (2016) Molecular cloning and characterization of a flavonoid O-methyltransferase with broad substrate specificity and regioselectivity from Citrus depressa. BMC Plant Biol 16:180.  https://doi.org/10.1186/s12870-016-0870-9 CrossRefGoogle Scholar
  18. Jin H, Xu Z, Cui K, Zhang T, Lu W, Huang J (2014) Dietary flavonoids fisetin and myricetin: dual inhibitors of Plasmodium falciparum falcipain-2 and plasmepsin II. Fitoterapia 94:55–61.  https://doi.org/10.1016/j.fitote.2014.01.017 CrossRefGoogle Scholar
  19. Jnawali NH, Lee E, Jeong KW, Shin A, Heo YS, Kim Y (2014) Anti-inflammatory activity of rhamnetin and a model of its binding to C-jun NH2-terminal kinase 1 and p38 MAPK. J Nat Prod 77:258–263.  https://doi.org/10.1021/np400803n CrossRefGoogle Scholar
  20. Jorge AP, Horst H, de Sousa E, Pizzolatti MG, Silva FR (2004) Insulinomimetic effects of kaempferitrin on glycaemia and on 14C-glucose uptake in rat soleus muscle. Chem Biol Interact 149:89–96.  https://doi.org/10.1016/j.cbi.2004.07.001 CrossRefGoogle Scholar
  21. Jose J, Dhanva AT, Haridas KR, Sumeshkumar TM, Javaraman S, Variyar EJ, Sudhakaran S (2016) Structural characterization of a novel derivative of myricetin from mimosa pudica as an anti-proliferative agent for the treatment of cancer. Biomed Pharmacother 84:1067–1077.  https://doi.org/10.1016/j.biopha.2016.10.020 CrossRefGoogle Scholar
  22. Jung HY, Lee D, Ryu HG, Choi BH, Go Y, Lee N, Son HG, Jeon J, Kim SH, Yoon JH, Sm p, Lee SV, Lee IK, Choi KY, Ryu SH, Nohara K, Yoo SH, Chen Z, Kim KT (2017) Myricetin improves endurance capacity and mitochondria I density by activating SIRT1 and PGC-1α. Sci Rep 7:6237.  https://doi.org/10.1038/s41598-017-05303-2 CrossRefGoogle Scholar
  23. Kaneko M, Hwang EI, Ohnishi Y, Horinouchi S (2003) Heterologous production of flavanones in Escherichia coli: potential for combinatorial biosynthesis of flavonoids in bacteria. J Ind Microbiol Biotechnol 30:456–461.  https://doi.org/10.1007/s10295-003-0061-1 CrossRefGoogle Scholar
  24. Kim DH, Kim BG, Lee Y, Ryu JY, Lim Y, Hur HG, Ahn JH (2005a) Regiospecific methylation of naringenin to ponciretin by soybean O-methyltransferase expressed in Escherichia coli. J Biotechnol 119:155–162.  https://doi.org/10.1016/j.jbiotec.2005.04.004 CrossRefGoogle Scholar
  25. Kim BG, Shin KH, Lee Y, Hur HG, Lim Y, Ahn JH (2005b) Multiple regiospecific methylations of a flavonoid by plant O-methyltransferases expressed in E. coli. Biotechnol Lett 27:1861–1864.  https://doi.org/10.1007/s10529-005-3893-0 CrossRefGoogle Scholar
  26. Kim JH, Shin KH, Ko JH, Ahn JH (2006a) Glycosylation of flavonols by Escherichia coli expressing glucosyltransferase from rice (Oryza sativa). J Biosci Bioeng 102:135–137.  https://doi.org/10.1263/jbb.102.135 CrossRefGoogle Scholar
  27. Kim BG, Kim H, Hur HG, Lim Y, Ahn JH (2006b) Regioselectivity of 7-O-methyltransferase of poplar to flavones. J Biotechnol 126:241–247.  https://doi.org/10.1016/j.jbiotec.2006.04.019 CrossRefGoogle Scholar
  28. Kim BG, Jung BR, Lee Y, Hur HG, Lim Y, Ahn JH (2006c) Regiospecific flavonoid 7-O-methylation with Streptomyces avermitilis O-methyltransferase expressed in Escherichia coli. J Agric Food Chem 54:823–828.  https://doi.org/10.1021/jf0522715 CrossRefGoogle Scholar
  29. Kim BG, Lee YJ, Lee S, Lim Y, Cheong Y, Ahn JH (2008) Altered regioselectivity of a poplar O-methyltransferase, POMT-7. J Biotechnol 138:107–111.  https://doi.org/10.1016/j.jbiotec.2008.08.007 CrossRefGoogle Scholar
  30. Kim BG, Sung SH, Jung NR, Chong Y, Ahn JH (2010) Biological synthesis of isorhamnetin 3-O-glucoside using engineered glucosyltransferase. J Mol Catal B Enzym 63:194–199.  https://doi.org/10.1016/j.molcatb.2010.01.012 CrossRefGoogle Scholar
  31. Kim S, Choi KJ, Cho SJ, Yun SM, Jeon JP, Koh YH, Song J, Johnson GV, Jo C (2016) Fisetin stimulates autophagic degradation of phosphorylated tau via the activation of TFEB and Nrf2 transcription factors. Sci Rep 6:24933.  https://doi.org/10.1038/srep24933 CrossRefGoogle Scholar
  32. Koirala N, Pandey RP, Parajuli P, Jung HJ, Sohng JK (2014) Methylation and subsequent glycosylation of 7,8-dihdroxyflavone. J Biotechnol 184:128–137.  https://doi.org/10.1016/j.jbiotec.2014.05.005 CrossRefGoogle Scholar
  33. Ku SK, Kim TH, Lee S, Kim SM, Bae JS (2013) Antithrombotic and profibrinolytic activities of isorhamnetin 3-O-galactoside and hyperoside. Food Chem Toxicol 53:197–204.  https://doi.org/10.1016/j.fct.2012.11.040 CrossRefGoogle Scholar
  34. Lee S, Sy S, Lee Y, Park Y, Kim BG, Ahn JH, Chong Y, Lee YH, Lim Y (2011) Rhamnetin production based on the rational design of the poplar O-methyltransferase enzyme and its biological activities. Bioorg Med Chem Lett 21:3866–3870.  https://doi.org/10.1016/j.bmcl.2011.05.043 CrossRefGoogle Scholar
  35. Lee SY, So YJ, Shin MS, Cho JY, Lee J (2014) Antibacterial effects of afzelin isolated from Cornus macrophylla on Pseudomonas aeruginosa, a leading cause of illness in immunocompromised individuals. Molecules 19:3173–3180.  https://doi.org/10.3390/molecules19033173 CrossRefGoogle Scholar
  36. Lee J, Choi JW, Sohng JK, Rp P, Park YI (2016) The immunostimulating activity of quercetin 3-O-xyloside in murine macrophages via activation of the ASK1/MAPK/NF-kB signaling pathway. Int Immunopharmacol 31:88–97.  https://doi.org/10.1016/j.intimp.2015.12.008 CrossRefGoogle Scholar
  37. Lee D, Park HL, Lee SW, Bhoo SH, Cho MH (2017) Biotechnological production of dimethoxyflavonoids using a fusion flavonoid O-methyltransferase possessing both 3′- and 7-O-methyltransferase activities. J Nat Prod 80:1467–1474.  https://doi.org/10.1021/acs.jnatprod.6b01164 CrossRefGoogle Scholar
  38. Lemmens KJ, Vrolijk MF, Bouwman FG, Van der Vijgh WJ, Bast A, Haenen GR (2014) The minor structural difference between the antioxidants quercetin and 4′-O-methylquercetin has a major impact on their thiol toxicity. Int J Mol Sci 15:7475–7484.  https://doi.org/10.3390/ijms15057475 CrossRefGoogle Scholar
  39. Li W, Hao J, Zhang L, Cheng Z, Deng X, Shu G (2017) Astragalin reduces hexokinase 2 through increasing MiR-125b to inhibit the proliferation of hepatocellular carcinoma cells in vitro and in vivo. J Agric Food Chem 65:5961–5972.  https://doi.org/10.1021/acs.jafc.7b02120 CrossRefGoogle Scholar
  40. Lim EK, Ashford DA, Hou B, Jackson RG, Bowles DJ (2004) Arabidopsis glycosyltransferases as biocatalysts in fermentation for regioselective synthesis of diverse quercetin glucosides. Biotechnol Bioeng 87:623–631.  https://doi.org/10.1002/bit.20154 CrossRefGoogle Scholar
  41. Ma XQ, Han T, Zhang X, Wu JZ, Rahman K, Quin LP, Zheng CJ (2015) Kaempferitrin prevents bone lost in ovariectomized rats. Phytomedicine 22:1159–1162.  https://doi.org/10.1016/j.phymed.2015.09.003 CrossRefGoogle Scholar
  42. Maher P, Akishi T, Abe K (2006) Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Proc Natl Acad Sci U S A103:16568–16573.  https://doi.org/10.1073/pnas.0607822103 CrossRefGoogle Scholar
  43. Malla S, Koffas MA, Kazlauskas RJ, Kim BG (2012) Production of 7-O-methyl aromadendrin, a medicinally valuable flavonoid, in Escherichia coli. Appl Environ Microbiol 78:684–694.  https://doi.org/10.1128/AEM.06274-11 CrossRefGoogle Scholar
  44. Marnon B, Sankar S, Lankalapalli RS, Anto JR (2015) Kaempferide, the most active among the four flavonoids isolated and characterized from Chromolaena odorata, induces apoptosis in cervical cancer cells while being pharmacologically safe. RSC Adv 5:100912–100922. https://doi.org/10.1039/C5RA19199HCrossRefGoogle Scholar
  45. Miyazaki Y, Ichimuta A, Sato S, Fujii T, Oishi S, Sakai H, Takeshima H (2018) The natural flavonoid myricetin inhibits gastric H+, K+-ATPase. Eur J Pharmacol 820:217–221.  https://doi.org/10.1016/j.ejphar.2017.12.042 CrossRefGoogle Scholar
  46. Moalin M, Van Strijdonck GP, Bast A, Haenen GR (2012) Competition between ascorbate and glutathione for the oxidized form of methylated quercetin metabolites and analogues: tamarixetin, 4′-methylquercetin, has the lowest thiol reactivity. J Agric Food Chem 60:9292–9297.  https://doi.org/10.1021/jf302068v CrossRefGoogle Scholar
  47. Mondal S, Jana J, Sengupta P, Jana S, Chatterjee S (2016) Myricetin arrests human telomeric G- quadruplex structure: a new mechanistic approach as an anticancer agent. Mol BioSyst 12:2506–2518.  https://doi.org/10.1039/c6mb00218h CrossRefGoogle Scholar
  48. Nath LR, Gorantla JN, Joseph SM, Antony J, Thankachan S, Menon DB, Sankar S, Lankalapalli RS, Anto RJ (2015) Kaempferide, the most active among the four flavonoids isolated and characterized from Chromolaena odorata, induces apoptosis in cervical cancer cells while being pharmacologically safe. RSC Adv 5. 100912-100922  https://doi.org/10.1039/C5RA19199H CrossRefGoogle Scholar
  49. Pandey RP, Malla S, Simkhada D, Kim BG, Sohng JK (2013) Production of 3-O-xylosyl quercetin in Escherichia coli. Appl Microbiol Biotechnol 97:1889–1901.  https://doi.org/10.1007/s00253-012-4438-9 CrossRefGoogle Scholar
  50. Pandey RP, Parajuli P, Chu LL, Darsandhari S, Sohng JK (2015) Biosynthesis of amino deoxy-sugar-conjugated flavonol glycosides by engineered Escherichia coli. Biochem Eng J 101:191–199.  https://doi.org/10.1016/j.bej.2015.05.017 CrossRefGoogle Scholar
  51. Pandey RP, Parajuli P, Koffas MAG, Sohng JK (2016a) Microbial production of natural and non-natural flavonoids: pathway engineering, directed evolution and systems/synthetic biology. Biotechnol Adv 34:634–662.  https://doi.org/10.1016/j.biotechadv.2016.02.012 CrossRefGoogle Scholar
  52. Pandey RP, Parajuli P, Chu Luan L, Kim SY, Sohng JK (2016b) Biosynthesis of novel fisetin glycoside from engineered Escherichia coli. J Ind Eng Chem 43:13–19.  https://doi.org/10.1186/s12934-015-0326-1 CrossRefGoogle Scholar
  53. Parajuli P, Pandey RP, Trang NT, Chaudhary AK, Sohng JK (2015) Synthetic sugar cassettes for the efficient production of flavonol glycosides in Escherichia coli. Microb Cell Factories 914:76.  https://doi.org/10.1186/s12934-015-0261-1 CrossRefGoogle Scholar
  54. Parajuli P, Pandey RP, Sohng JK (2018) Regiospecific biosynthesis of tamarixetin derivatives in Escherichia coli. Biochem Eng J 133:113–121.  https://doi.org/10.1016/j.bej.2018.02.004 CrossRefGoogle Scholar
  55. Park JY, Kim SI, Lee HJ, Kim SS, Kwon YS, Chun W (2016) Isorhamnetin 3-O-glucuronide suppresses JNK and p38 activation and increases heme-oxygenase-1 in lipopolysaccharide challenged RAW264.7 cells. Drug Dev Res 77:143–151.  https://doi.org/10.1002/ddr.21301 CrossRefGoogle Scholar
  56. Pasetto S, Pardi V, Murata RM (2014) Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dualchamber in vitro model. PLoS One 9:e115323.  https://doi.org/10.1371/journal.pone.0115323 CrossRefGoogle Scholar
  57. Pei J, Dong P, Wu T, Zhao L, Fang X, Cao F, Tang F, Yue Y (2016) Metabolic engineering of Escherichia coli for astragalin biosynthesis. J Agric Food Chem 64:7966–7972.  https://doi.org/10.1021/acs.jafc.6b03447 CrossRefGoogle Scholar
  58. Philchenkov AA, Zavelevych MP (2015) Rhamnazin inhibits proliferation and induces apoptosis of human jurkat leukemia cells in vitro. Ukr Biochem J 87:122–128.  https://doi.org/10.15407/ubj87.06.122 CrossRefGoogle Scholar
  59. Phillips PA, Sangwan V, Borja-cacho D, Dudeja V, Vickers SM, Saluja A (2011) Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Cancer Lett 308:181–188.  https://doi.org/10.1016/j.canlet.2011.05.002 CrossRefGoogle Scholar
  60. Plaza M, Pozzo T, Liu J, Ara KZG, Turner C, Karlsson EN (2014) Substituent effects on in vitro antioxidizing properties, stability, and solubility in flavonoids. J Agric Food Chem 62:3321–3333.  https://doi.org/10.1021/jf405570u CrossRefGoogle Scholar
  61. Qiu X, Kroeker A, He S, Kozak R, Audet J, Mbikay M, Chretien M (2016) Prophylactic efficacy of quercetin 3-O-β-D-glucoside against Ebola virus infection. Antimicrob Agents Chemother 60:5182–5188.  https://doi.org/10.1128/AAC.00307-16 CrossRefGoogle Scholar
  62. Qu D, Han J, Ren H, Yang W, Zhang X, Zheng W, Wang D (2016) Cardio protective effects of astragalin against myocardial ischemia/reperfusion injury in isolated rat heart. Oxidative Med Cell Longev 2016:8194690.  https://doi.org/10.1155/2016/8194690 CrossRefGoogle Scholar
  63. Ramalho SD, de Sousa LR, Burger MC, Lima MI, da Silva MF, Fernandes JB, Vieira PC (2015) Evaluation of flavonols and derivatives as human cathepsin B inhibitor. Nat Prod Res 29:2212–2214.  https://doi.org/10.1080/14786419.2014.1002404 CrossRefGoogle Scholar
  64. Saito K, Yonekura-Sakakibara K, Nakabayashi R, Higashi Y, Yamazaki M, Tohge T, Fernje AR (2013) The flavonoid biosynthetic pathway in Arabidopsis: structural and genetic diversity. Plant Physiol Biochem 72:21–34.  https://doi.org/10.1016/j.plaphy.2013.02.001 CrossRefGoogle Scholar
  65. Shin SW, Jung E, Kim S, Kim JH, Kim EG, Lee J, Park D (2013) Antagonizing effects and mechanisms of afzelin against UVB-induced cell damage. PLoS One 8:e61971.  https://doi.org/10.1371/journal.pone.0061971 CrossRefGoogle Scholar
  66. Simkhada D, Lee HC, Sohng JK (2010) Genetic engineering approach for the production of rhamnosyl and allosyl flavonoids from Escherichia coli. Biotechnol Bioeng 107:154–162.  https://doi.org/10.1002/bit.22782 CrossRefGoogle Scholar
  67. Song JH, Shim JK, Choi HJ (2011) Quercetin 7-rhamnoside reduces porcine epidemic diarrhea virus replication via independent pathway of viral induced reactive oxygen species. Virol J 8:460.  https://doi.org/10.1186/1743-422X-8-460 CrossRefGoogle Scholar
  68. Stahlhut SG, Siedler S, Malla S, Harrison SJ, Maury J, Neves AR, Forster J (2015) Assembly of a novel biosynthetic pathway for production of the plant flavonoid fisetin in Escherichia coli. Metab Eng 31:84–93.  https://doi.org/10.1016/j.ymben.2015.07.002 CrossRefGoogle Scholar
  69. Thuan NH, Rp P, Thuy TT, Park JW, Sohng JK (2013) Improvement of region-specific production of myricetin-3-O-α-L-rhamnoside in engineered Escherichia coli. Appl Biochem Biotechnol 171:1956–1967.  https://doi.org/10.1007/s12010-013-0459-9 CrossRefGoogle Scholar
  70. Xiao R, Xiang AL, Pang HB, Liu KQ (2017) Hyperoside protects against hypoxia/reoxygenation induced injury in cardiomyocytes by suppressing the BniP3 expression. Gene 629:86–91.  https://doi.org/10.1016/j.gene.2017.07.063 CrossRefGoogle Scholar
  71. Xue W, Song BA, Zhao HJ, Qi XB, Huang YJ, Liu XH (2015) Novel myricetin derivatives; design, synthesis and anticancer activity. Eur J Med Chem 97:155–163.  https://doi.org/10.1016/j.ejmech.2015.04.063 CrossRefGoogle Scholar
  72. Yadav DK, Bhartkar YP, Hazra A, Pal U, Berma S, Jana S, Singh UP, Maiti NC, Mondal NB, Swarnakar S (2017) Tamarixetin 3-O-β-D-glucopyranoside from Azadirachta indica leaves: Gastroprotective role through inhibition of matrix metalloproteinase-9 activity in mice. J Nat Prod 80:1347–1353.  https://doi.org/10.1021/acs.jnatprod.6b00957 CrossRefGoogle Scholar
  73. Yoon Y, Yi YS, Lee Y, Kim S, Kim BG, Ahn JH, Lim Y (2005) Characterization of O-methyltransferase ScOMT1 cloned from Streptomyces coelicolor A3 (2). Biochim Biophys Acta 1730:85–95.  https://doi.org/10.1016/j.bbaexp.2005.06.005 CrossRefGoogle Scholar
  74. Yoon Y, Park Y, Lee Y, Yi YS, Park JC, Ahn JH, Lim Y (2010) Characterization of an O-methyltransferase from Streptomyces avermitilis MA-4680. J Microbiol Biotechnol 20:1359–1366CrossRefGoogle Scholar
  75. Yoon JA, Kim BG, Lee WJ, Lim Y, Chong Y, Ahn JH (2012) Production of a novel quercetin glycoside through metabolic engineering of Escherichia coli. Appl Environ Microbiol 78:4256–4262.  https://doi.org/10.1128/AEM.00275-12 CrossRefGoogle Scholar
  76. Yu Y, Cai W, Pei CG, Shao Y (2015) Rhamnazin, a novel inhibitor of VEGFR2 signaling with potent antiangiogenic activity and antitumor efficacy. Biochem Biophys Res Commun 458:913–919.  https://doi.org/10.1016/j.bbrc.2015.02.059 CrossRefGoogle Scholar
  77. Zhang X, Liu CJ (2015) Multifaceted regulations of gateway enzyme phenylalanine ammonia-lyase in the biosynthesis of phenylpropanoids. Mol Plant 8:17–27.  https://doi.org/10.1016/j.molp.2014.11.001 CrossRefGoogle Scholar
  78. Zhang N, Ying MD, Wu YP, Zhou ZH, Ye ZM, Li H, Lin DS (2014) Hyperoside, a flavonoid compound, inhibits proliferation and stimulates osteogenic differentiation of human osteosarcoma cells. PLoS One 9:e98973.  https://doi.org/10.1371/journal.pone.0098973 CrossRefGoogle Scholar
  79. Zhang W, Lu X, Wang W, Ding Z, Fu Y, Zhou X, Zhang N, Cao Y (2017) Inhibitory effects of emodin, thymol, and astragalin on Leptospira interrogans-induced inflammatory response in the uterine and endometrium epithelial cells of mice. Inflammation 40:666–675.  https://doi.org/10.1007/s10753-017-0513-9 CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Prakash Parajuli
    • 1
  • Biplav Shrestha
    • 1
  • Jae Kyung Sohng
    • 1
    • 2
  • Ramesh Prasad Pandey
    • 1
    • 2
  1. 1.Department of Life Science and Biochemical EngineeringSun Moon UniversityAsan-siRepublic of Korea
  2. 2.Department of Pharmaceutical Engineering and BiotechnologySun Moon UniversityAsan-siRepublic of Korea

Personalised recommendations