Miraculin

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Miraculin Glycoprotein
Miraculin.png
Crystallographic structure of a dimeric miraculin-like protein from seeds of Murraya koenigii.[1]
Identifiers
SymbolMIRA_RICDU
UniProtP13087

Miraculin is a taste modifier, a glycoprotein extracted from the fruit of Synsepalum dulcificum.[2] The berry, also known as the miracle fruit, was documented by explorer Chevalier des Marchais, who searched for many different fruits during a 1725 excursion to its native West Africa.

Miraculin itself is not sweet. After the taste buds are exposed to miraculin (which binds to sweet receptors on the tongue), acidic foods that are ordinarily sour (such as citrus) are perceived as sweet.[2][3] This effect lasts up to about an hour.[4][5] The active substance was named miraculin after its extraction was published in 1968.[6]

Glycoprotein structure[edit]

Miraculin was first sequenced in 1989 and was found to be a glycoprotein consisting of 191 amino acids and some carbohydrate chains.[7]

Miraculin occurs as a tetramer (98.4 kDa), a combination of 4 monomers group by dimer. Within each dimer 2 miraculin glycoproteins are linked by a disulfide bridge.[8]

SIGNAL (29) MKELTMLSLS FFFVSALLAA AANPLLSAA
1-50 DSAPNPVLDI DGEKLRTGTN YYIVPVLRDH GGGLTVSATT PNGTFVCPPR
51-100 VVQTRKEVDH DRPLAFFPEN PKEDVVRVST DLNINFSAFM PNPGPETISS
101-150 WCRWTSSTVW RLDKYDESTG QYFVTIGGVK FKIEEFCGSG FYKLVFCPTV
151-191 CGSCKVKCGD VGIYIDQKGR GRRLALSDKP FAFEFNKTVY F
Amino acids sequence of glycoprotein miraculin unit adapted from Swiss-Prot biological database of protein sequences.[9]

The molecular weight of the glycoprotein is 24.6 kDa including 3.4 kDa (13.9% of the weight) of sugar constituted (on molar ratio) of glucosamine (31%), mannose (30%), fucose (22%), xylose (10%) and galactose (7%).[2]

The taste-modifying protein, miraculin, has seven cystein residues in a molecule composed of 191 amino acid residues. Both tetramer miraculin and native dimer miraculin in its crude state have the taste-modifying activity of turning sour tastes into sweet tastes.[10]

Sweetness properties[edit]

Miraculin, unlike curculin (another taste-modifying agent),[11] is not sweet by itself, but it can change the perception of sourness to sweetness, even for a long period after consumption.[4] The duration and intensity of the sweetness-modifying effect depends on various factors, such as miraculin concentration, duration of contact of the miraculin with the tongue, and acid concentration.[3][4] Maximum sweet-induced response has been shown to be equivalent to the sweetness of 17% sucrose solution.[citation needed] Glycoprotein is also sensitive to heat. When heated over 100 °C, miraculin loses its taste-modifying property. Miraculin activity is inactivated at pH below 3 and pH above 12 at room temperature.[4]

Although the detailed mechanism of the taste-inducing behavior is unknown, it appears the sweet receptors are activated by acids which are related to sourness, an effect remaining until the taste buds perceive a neutral pH.[3][4] Sweeteners are perceived by the human sweet taste receptor, hT1R2-hT1R3, which belongs to G protein-coupled receptors,[4] modified by the two histidine residues (i.e. His30 and His60) which participate in the taste-modifying behavior.[12] One site maintains the attachment of the protein to the membranes while the other (with attached xylose or arabinose) activates the sweet receptor membrane in acid solutions.[8]

As a sweetener[edit]

As miraculin is a readily soluble protein and relatively heat stable, it is a potential sweetener in acidic food (e.g. soft drinks). While attempts to express it in yeast and tobacco plants have failed, researchers have succeeded in preparing genetically modified E. coli bacteria,[13] lettuce[14] and tomatoes[15] that express miraculin. The scientists' crops resulted in 40 micrograms of miraculin per gram of lettuce leaves, with two grams of lettuce leaves producing roughly the same amount of miraculin as in one miracle fruit berry.[16]

The use of miraculin as a food additive was forbidden in 1974 by the United States Food and Drug Administration, in circumstances that have been interpreted as suggesting influence by competing commercial interests.[17][18] Since 2011, The FDA has imposed a ban on importing Synsepalum dulcificum (specifying 'miraculin') from its origin in Taiwan, declaring it as an "illegal undeclared sweetener".[19] Although this ban does not apply to fresh and freeze-dried miracle fruit, the fresh or normally-frozen berry deteriorates rapidly. The ban also does not apply to sale as a dietary supplement.[20] There is informed opinion that the FDA ban could be overturned given sufficient funding for the required safety studies.[17] Miraculin has a novel food status in the European Union.[21] It is approved in Japan as a safe food additive, according to the List of Existing Food Additives published by the Ministry of Health and Welfare (published by JETRO).

See also[edit]

References[edit]

  1. ^ PDB: 3IIR​; Gahloth D, Selvakumar P, Shee C, Kumar P, Sharma AK (February 2010). "Cloning, sequence analysis and crystal structure determination of a miraculin-like protein from Murraya koenigii". Archives of Biochemistry and Biophysics. 494 (1): 15–22. doi:10.1016/j.abb.2009.11.008. PMID 19914199.
  2. ^ a b c Theerasilp S, Kurihara Y (August 1988). "Complete purification and characterization of the taste-modifying protein, miraculin, from miracle fruit". The Journal of Biological Chemistry. 263 (23): 11536–9. PMID 3403544.
  3. ^ a b c Sanematsu K, Kitagawa M, Yoshida R, Nirasawa S, Shigemura N, Ninomiya Y (March 2016). "Intracellular acidification is required for full activation of the sweet taste receptor by miraculin". Scientific Reports. 6: 22807. Bibcode:2016NatSR...622807S. doi:10.1038/srep22807. PMC 4785348. PMID 26960429.
  4. ^ a b c d e f Koizumi A, Tsuchiya A, Nakajima K, Ito K, Terada T, Shimizu-Ibuka A, Briand L, Asakura T, Misaka T, Abe K (October 2011). "Human sweet taste receptor mediates acid-induced sweetness of miraculin". Proceedings of the National Academy of Sciences of the United States of America. 108 (40): 16819–24. Bibcode:2011PNAS..10816819K. doi:10.1073/pnas.1016644108. PMC 3189030. PMID 21949380.
  5. ^ Swamy KB, Hadi SA, Sekaran M, Pichika MR (November 2014). "The clinical effects of Synsepalum dulcificum: a review". Journal of Medicinal Food. 17 (11): 1165–9. doi:10.1089/jmf.2013.3084. PMID 25314134.
  6. ^ Kurihara K, Beidler LM (September 1968). "Taste-modifying protein from miracle fruit". Science. 161 (3847): 1241–3. Bibcode:1968Sci...161.1241K. doi:10.1126/science.161.3847.1241. PMID 5673432.
  7. ^ Theerasilp S, Hitotsuya H, Nakajo S, Nakaya K, Nakamura Y, Kurihara Y (April 1989). "Complete amino acid sequence and structure characterization of the taste-modifying protein, miraculin". The Journal of Biological Chemistry. 264 (12): 6655–9. PMID 2708331.
  8. ^ a b Kurihara Y (1992). "Characteristics of antisweet substances, sweet proteins, and sweetness-inducing proteins". Critical Reviews in Food Science and Nutrition. 32 (3): 231–52. doi:10.1080/10408399209527598. PMID 1418601.
  9. ^ UniProtKB/Swiss-Prot database entry P13087
  10. ^ Igeta H, Tamura Y, Nakaya K, Nakamura Y, Kurihara Y (September 1991). "Determination of disulfide array and subunit structure of taste-modifying protein, miraculin". Biochimica et Biophysica Acta. 1079 (3): 303–7. doi:10.1016/0167-4838(91)90073-9. PMID 1911854.
  11. ^ Kurimoto E, Suzuki M, Amemiya E, Yamaguchi Y, Nirasawa S, Shimba N, Xu N, Kashiwagi T, Kawai M, Suzuki E, Kato K (November 2007). "Curculin exhibits sweet-tasting and taste-modifying activities through its distinct molecular surfaces". The Journal of Biological Chemistry. 282 (46): 33252–6. doi:10.1074/jbc.C700174200. PMID 17895249.
  12. ^ Ito K, Asakura T, Morita Y, Nakajima K, Koizumi A, Shimizu-Ibuka A, Masuda K, Ishiguro M, Terada T, Maruyama J, Kitamoto K, Misaka T, Abe K (August 2007). "Microbial production of sensory-active miraculin". Biochemical and Biophysical Research Communications. 360 (2): 407–11. doi:10.1016/j.bbrc.2007.06.064. PMID 17592723.
  13. ^ Matsuyama T, Satoh M, Nakata R, Aoyama T, Inoue H (April 2009). "Functional expression of miraculin, a taste-modifying protein in Escherichia coli". Journal of Biochemistry. 145 (4): 445–50. doi:10.1093/jb/mvn184. PMID 19122203.
  14. ^ Sun HJ, Cui ML, Ma B, Ezura H (January 2006). "Functional expression of the taste-modifying protein, miraculin, in transgenic lettuce". FEBS Letters. 580 (2): 620–6. doi:10.1016/j.febslet.2005.12.080. PMID 16406368.
  15. ^ Kato K, Yoshida R, Kikuzaki A, Hirai T, Kuroda H, Hiwasa-Tanase K, Takane K, Ezura H, Mizoguchi T (September 2010). "Molecular breeding of tomato lines for mass production of miraculin in a plant factory". Journal of Agricultural and Food Chemistry. 58 (17): 9505–10. doi:10.1021/jf101874b. PMID 20695489.
  16. ^ Slater, Joanna (2007-03-30). "To Make Lemons Into Lemonade, Try 'Miracle Fruit'". Wall Street Journal. Retrieved 2008-05-28. [...]two grams produce roughly the same effect as one miracle fruit.
  17. ^ a b Cox, David (2014-05-29). "The 'Miracle' Berry That Could Replace Sugar". The Atlantic Monthly Group. Retrieved 2018-02-25.
  18. ^ Gollner, Adam Leith (31 March 2009). The Fruit Hunters: A Story of Nature, Adventure, Commerce and Obsession. Anchor Canada. ISBN 978-0385662680.
  19. ^ "Synsepalum dulcificum Import Alert 45-07; Taiwan". US Food and Drug Administration. 5 February 2018. Retrieved 9 February 2018.
  20. ^ Hieggelke, Brian (2013-04-18). "Sugar Freedom: Chef Homaro Cantu and his Magnificent Miracle Berry Obsession". NewCity Communications Inc. Retrieved 2018-02-25.
  21. ^ "Novel Food Catalogue". Retrieved 2 July 2013.