Applied Microbiology and Biotechnology

, Volume 83, Issue 1, pp 27–34 | Cite as

Biosynthesis and biotechnological production of serotonin derivatives

  • Kiyoon Kang
  • Sangkyu Park
  • Young Soon Kim
  • Sungbeom Lee
  • Kyoungwhan Back
Mini-Review

Abstract

Serotonin derivatives belong to a class of phenylpropanoid amides found at low levels in a wide range of plant species. Representative serotonin derivatives include feruloylserotonin (FS) and 4-coumaroylserotonin (CS). Since the first identification of serotonin derivatives in safflower seeds, their occurrence, biological significance, and pharmacological properties have been reported. Recently, serotonin N-hydroxycinnamoyl transferase (SHT), which is responsible for the synthesis of serotonin derivatives, was cloned from pepper (Capsicum annuum) and characterized in terms of its enzyme kinetics. Using the SHT gene, many attempts have been made to either increase the level of serotonin derivatives in transgenic plants or produce serotonin derivatives de novo in microbes by dual expression of key genes such as SHT and 4-coumarate-CoA ligase (4CL). Due to the strong antioxidant activity and other therapeutic properties of serotonin derivatives, these compounds may have high potential in treatment and prophylaxis, as cosmetic ingredients, and as major components of functional foods or feeds that have health-improving effects. This review examines the biosynthesis of serotonin derivatives, corresponding enzymes, heterologous production in plants or microbes, and their applications.

Keywords

Antioxidant Caffeoylserotonin Feruloylserotonin 4-Coumaroylserotonin Serotonin derivatives 

References

  1. Choi SW, Park RW, Lee WJ (2002) Novel use of polyphenol compounds isolated from safflower (Carthamus tincorious L.) seeds. Korea patent 10-0354791-0000Google Scholar
  2. Ehlting J, Büttner D, Wang Q, Douglas CJ, Somssich IE, Kombrink E (1999) Three 4-coumarate:coenzyme A ligases in Arabidopsis thaliana represent two evolutionarily divergent classes in angiosperms. Plant J 19:9–20CrossRefGoogle Scholar
  3. Facchini PJ, Hagel J, Zulak KG (2002) Hydroxycinnamic acid amide metabolism: physiology and biochemistry. Can J Bot 80:577–589CrossRefGoogle Scholar
  4. Geerlings A, Redondo FJ, Contin A, Memelink J, van der Heijden R, Verpoorte R (2001) Biotransformation of tryptamine and secologanin into plant terpenoid indole alkaloids by transgenic yeast. Appl Microbiol Biotechnol 56:420–424CrossRefGoogle Scholar
  5. Guillet G, De Luca V (2005) Wound-inducible biosynthesis of phytoalexin hydroxycinnamic acid amides of tyramine in tryptophan and tyrosine decarboxylase transgenic tobacco lines. Plant Physiol 137:692–699CrossRefGoogle Scholar
  6. Hagel JM, Facchini PJ (2005) Elevated tyrosine decarboxylase and tyramine hydroxycinnamoyltransferase levels increase wound-induced tyramine-derived hydroxycinnamic acid amide accumulation in transgenic tobacco leaves. Planta 221:904–914CrossRefGoogle Scholar
  7. Hotta Y, Nagatsu A, Liu W, Muto T, Narumiya C, Lu X, Yajima M, Ishikawa N, Miyazeki K, Kawai N, Mizukami H, Sakakibara J (2002) Protective effects of antioxidative serotonin derivatives isolated from safflower against postischemic myocardial dysfunction. Mol Cell Biochem 238:151–162CrossRefGoogle Scholar
  8. Ishihara A, Kawata N, Matsukawa T, Iwamura H (2000) Induction of N-hydroxycinnamoyltyramine synthesis and tyramine N-hydroxycinnamoyltransferase (THT) activity by wounding in maize leaves. Biosci Biotechnol Biochem 64:1025–1031CrossRefGoogle Scholar
  9. Ishihara A, Hashimoto Y, Tanaka C, Dubouzet JG, Nakao T, Matsuda F, Nishioka T, Miyagawa H, Wakasa K (2008) The tryptophan pathway is involved in the defense responses of rice against pathogenic infection via serotonin production. Plant J 54:481–495CrossRefGoogle Scholar
  10. Jang SM, Ishihara A, Back K (2004) Production of coumaroylserotonin and feruloylserotonin in transgenic rice expressing pepper hydroxycinnamoyl-coenzyme A:serotonin N-(hydroxycinnamoyl) transferase. Plant Physiol 135:346–356CrossRefGoogle Scholar
  11. Jenett-Siems K, Weigl R, Kaloga M, Schulz J, Eich E (2003) Ipobscurines C and D: macrolactam-type indole alkaloids from the seeds of Ipomoea obscura. Phytochemistry 62:1257–1263CrossRefGoogle Scholar
  12. Kang S, Back K (2006) Enriched production of N-hydroxycinnamic acid amides and biogenic amines in pepper (Capsicum annuum) flowers. Sci Hortic 108:337–341CrossRefGoogle Scholar
  13. Kang K, Back K (2009) Production of phenylpropanoid amides in recombinant Escherichia coli. Metab Eng 11:64–68CrossRefGoogle Scholar
  14. Kang K, Jang SM, Kang S, Back K (2005) Enhanced neutraceutical serotonin derivatives of rice seed by hydroxycinnamoyl-CoA:serotonin N-(hydroxycinnamoyl) transferase. Plant Sci 168:783–788CrossRefGoogle Scholar
  15. Kang S, Kang K, Chung GC, Choi D, Ishihara A, Lee DS, Back K (2006) Functional analysis of the amine substrate specificity domain of pepper tyramine and serotonin N-hydroxycinnamoyltransferases. Plant Physiol 140:704–715CrossRefGoogle Scholar
  16. Kang S, Kang K, Lee K, Back K (2007a) Characterization of rice tryptophan decarboxylases and their direct involvement in serotonin biosynthesis in transgenic rice. Planta 227:263–272CrossRefGoogle Scholar
  17. Kang S, Kang K, Lee K, Back K (2007b) Characterization of tryptamine 5-hydroxylase and serotonin synthesis in rice plants. Plant Cell Rep 26:2009–2015CrossRefGoogle Scholar
  18. Kang K, Lee K, Sohn SO, Park S, Lee S, Kim SY, Kim YS, Back K (2009) Ectopic expression of serotonin N-hydroxycinnamoyltransferase and different production of phenylpropanoid amides in transgenic tomato tissues. Sci Hortic doi:1016/j.scienta.2008.12.015
  19. Koyama N, Kuribayashi K, Seki T, Kobayashi K, Furuhata Y, Suzuki K, Arisaka H, Nakano T, Amino Y, Ishii K (2006) Serotonin derivatives, major safflower (Carthamus tinctorius L.) seed antioxidants, inhibit low-density lipoprotein (LDL) oxidation and atherosclerosis in apolipoprotein E-deficient mice. J Agric Food Chem 54:4970–4976CrossRefGoogle Scholar
  20. Koyama N, Kuribayashi K, Ishii K, Kobayashi K (2009) Composition for preventing atherosclerosis. US patent 07,485,328Google Scholar
  21. Kumarasamy Y, Middleton M, Reid RG, Nahar L, Sarker SD (2003) Biological activity of serotonin conjugates from the seeds of Centaurea nigra. Fitoterapia 74:609–612CrossRefGoogle Scholar
  22. Lee DG, Park Y, Kim MR, Jung HJ, Seu YB, Hahm KS, Woo ER (2004) Anti-fungal effects of phenolic amides isolated from the root bark of Lycium chinense. Biotechnol Lett 26:1125–130CrossRefGoogle Scholar
  23. Lee K, Kang K, Park M, Woo YM, Back K (2008) Endosperm-specific expression of serotonin N-hydroxycinnamoyltransferase in rice. Plant Foods Hum Nutr 63:53–57CrossRefGoogle Scholar
  24. Ly D, Kang K, Choi JY, Ishihara A, Back K, Lee SG (2008) HPLC analysis of serotonin, tryptamine, tyramine, and the hydroxycinnamic acid amides of serotonin and tyramine in food vegetables. J Med Food 11:385–389CrossRefGoogle Scholar
  25. Martin-Tanguy J (1985) The occurrence and possible function of hydroxycinnamoyl acid amides in plants. Plant Growth Regul 3:381–399CrossRefGoogle Scholar
  26. Mijts BN, Schmidt-Dannert C (2003) Engineering of secondary metabolite pathways. Curr Opin Biotechnol 14:597–602CrossRefGoogle Scholar
  27. Murch SJ, KrishnaRaj S, Saxena PK (2000) Tryptophan is a precursor for melatonin and serotonin biosynthesis in in vitro regenerated St. John’s wort (Hypericum perforatum L. cv. Anthos) plants. Plant Cell Rep 19:698–704CrossRefGoogle Scholar
  28. Nagatsu A, Zhang HL, Mizukami H, Okuyama H, Sakakibara J, Tokuda H, Nishino H (2000) Tyrosinase inhibitory and anti-tumor promoting activities of compounds isolated from safflower (Carthamus tinctorius L.) and cotton (Gossypium hirsutum L.) oil cakes. Nat Prod Lett 14:153–158Google Scholar
  29. Niwa T, Etoh H, Shimizu A, Shimizu Y (2000) Cis-N-(p-coumaroyl) serotonin from konnyaku, Amorphophallus konjac K. Koch. Biosci Biotechnol Biochem 64:2269–2271CrossRefGoogle Scholar
  30. Noé W, Mollenschott C, Berlin J (1984) Tryptophan decarboxylase from Catharanthus roseus cell suspension cultures: purification, molecular and kinetic data of the homogenous protein. Plant Mol Biol 3:281–288CrossRefGoogle Scholar
  31. Park JB (2008) Serotomide and safflomide modulate forskolin-stimulated cAMP formation via 5-HT1 receptor. Phytomedicine 15:1093–1098CrossRefGoogle Scholar
  32. Park JB, Schoene N (2002) Synthesis and characterization of N-coumaroyltyramine as a potent phytochemical which arrests human transformed cells via inhibiting protein tyrosine kinases. Biochem Biophys Res Commun 292:1104–1110CrossRefGoogle Scholar
  33. Park M, Kang K, Park S, Back K (2008a) Conversion of 5-hydroxytryptophan into serotonin by tryptophan decarboxylase in plants, Escherichia coli, and yeast. Biosci Biotechnol Biochem 72:2456–2458CrossRefGoogle Scholar
  34. Park M, Kang K, Park S, Kim YS, Ha SH, Lee SW, Ahn MJ, Bae JM, Back K (2008b) Expression of serotonin derivative synthetic genes on a single self-processing polypeptide and the production of serotonin derivatives in microbes. Appl Microbiol Biotechnol 81:43–49CrossRefGoogle Scholar
  35. Pavlík M, Laudová V, Grüner K, Vokáč K, Harmatha J (2002) High-performance liquid chromatographic analysis and separation of N-feruloylserotonin isomers. J Chromatogr 770:291–295CrossRefGoogle Scholar
  36. RadWanski ER, Last RL (1995) Tryptophan biosynthesis and metabolism: biochemical and molecular genetics. Plant Cell 7:921–934CrossRefGoogle Scholar
  37. Roh JS, Han JY, Kim JH, Hwang JK (2004) Inhibitory effects of active compounds isolated from safflower (Carthamus tinctorius L.) seeds for melanogenesis. Biol Pharm Bull 27:1976–1978CrossRefGoogle Scholar
  38. Ryan MD, King AMQ, Thomas GP (1991) Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues located within a 19 amino acid sequence. J Gen Virol 72:2727–2732CrossRefGoogle Scholar
  39. Sakamura S, Terayama Y, Kawakatsu S, Ichihara A, Saito H (1978) Conjugated serotonins related to cathartic activity in safflower seed (Carthamus tinctorius L.). Agric Biol Chem 42:1805–1806Google Scholar
  40. Sarker SD, Laird A, Nahar L, Kumarasamy Y, Jaspars M (2001) Indole alkaloids from the seeds of Centaurea cyanus (Asteraceae). Phytochemistry 57:1273–1276CrossRefGoogle Scholar
  41. Schröder P, Abele C, Gohr P, Stuhlfauth-Roisch U, Grosse W (1999) Latest on the enzymology of serotonin biosynthesis in walnut seeds. Adv Exp Med Biol 467:637–644Google Scholar
  42. Shoeb M, MacManus S, Jaspars M, Trevidu J, Nahar L, Kong-Thoo-Lin P, Sarker SD (2006) Montamine, a unique dimeric indole alkaloid, from the seeds of Centaurea montana (Asteraceae), and its in vitro cytotoxic activity against the CaCo2 colon cancer cells. Tetrahedron 62:11172–11177CrossRefGoogle Scholar
  43. Takii T, Hayashi M, Hiroma H, Chiba T, Kawashima S, Zhang HL, Nagatsu A, Sakakibara J, Onozaki K (1999) Serotonin derivative, N-(p-coumaroyl) serotonin, isolated from safflower (Carthamus tinctorius L.) oil cake augments the proliferation of normal human and mouse fibroblasts in synergy with basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF). J Biochem 125:910–915Google Scholar
  44. Takii T, Kawashima S, Chiba T, Hayashi H, Hayashi M, Hiroma H, Kimura H, Inukai Y, Shibata Y, Nagatsu A, Sakakibara J, Oomoto Y, Hirose K, Onozaki K (2003) Multiple mechanisms involved in the inhibition of proinflammatory cytokine production from human monocytes by N-(p-coumaroyl) serotonin and its derivatives. Immunopharmacology 3:273–277CrossRefGoogle Scholar
  45. Tanaka E, Tanaka C, Mori N, Kuwahara Y, Tsuda M (2003) Phenylpropanoid amides of serotonin accumulate in witchs’ broom diseased bamboo. Phytochemistry 64:965–969CrossRefGoogle Scholar
  46. Tozawa Y, Hasegawa H, Teruhiko T, Wakasa K (2001) Characterization of rice anthranilate synthase α-subunit genes OASA1 and OASA2. Tryptophan accumulation in transgenic rice expressing a feedback-insensitive mutant OASA1. Plant Physiol 126:1493–1506CrossRefGoogle Scholar
  47. Watanabe M (1999) Antioxidative phenolic compounds from Japanese barnyard millet (Echinochloa utilis) grains. J Agric Food Chem 47:4500–4505CrossRefGoogle Scholar
  48. Wink M (1997) Special nitrogen metabolism. In: Dey PM, Harborne JB (eds) Plant Biochemistry. Academic, San Diego, pp 439–486CrossRefGoogle Scholar
  49. Yamamotová A, Pometlova M, Harmatha J, Raskova H, Rokyta R (2007) The selective effect of N-feruloylserotonins isolated from Leuzea carthamoides on nociception and anxiety in rats. J Ethnopharm 112:368–374CrossRefGoogle Scholar
  50. Yuji N, Naoto K, Katsuya S, Hideaki K, Yuka I (2007) Anti-inflammatory composition. PCT patent 2007129743Google Scholar
  51. Zhang HL, Nagatsu A, Sakakibara J (1996) Novel antioxidants from safflower (Carthamus tinctorius L.) oil cake. Chem Pharm Bull 44:874–876Google Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Kiyoon Kang
    • 1
  • Sangkyu Park
    • 2
  • Young Soon Kim
    • 1
  • Sungbeom Lee
    • 3
  • Kyoungwhan Back
    • 1
  1. 1.Department of Biotechnology, Agricultural Plant Stress Research CenterChonnam National UniversityGwangjuRepublic of Korea
  2. 2.Interdisciplinary Program for Bioenergy and Biomaterials of Graduate SchoolChonnam National UniversityGwangjuKorea
  3. 3.Biological SciencesVirginia TechBlacksburgUSA

Personalised recommendations