Miraculin is a taste modifier, a glycoprotein extracted from the fruit of Synsepalum dulcificum. 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 does not taste sweet. When taste buds are exposed to miraculin, the protein binds to the sweetness receptors. This causes normally sour-tasting acidic foods, such as citrus, to be perceived as sweet. The effect lasts up to about an hour.
The sweetening properties of Synsepalum dulcificum berries were first noted by des Marchais during expeditions to West Africa in the 18th century. The term miraculin derived from experiments to isolate and purify the active glycoprotein that gave the berries their sweetening effects, results that were published simultaneously by Japanese and Dutch scientists working independently in the 1960s (the Dutch team called the glycoprotein mieraculin). The word miraculin was in common use by the mid-1970s.
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.
The native state of miraculin is a tetramer consisting of two dimers, each held together by a disulfide bridge. Both tetramer miraculin and native dimer miraculin in its crude state have the taste-modifying activity of turning sour tastes into sweet tastes. Miraculin belongs to the Kunitz STI protease inhibitor family.
Miraculin, unlike curculin (another taste-modifying agent), is not sweet by itself, but it can change the perception of sourness to sweetness, even for a long period after consumption. 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. Miraculin reaches its maximum sweetness with a solution containing at least 4*10−7 mol/l miraculin, which is held in the mouth for about 3 minutes. Maximum is equivalent in sweetness to a 0.4 mol/l solution of sucrose. Miraculin degrades permanently via denaturation at high temperatures, at pH below 3 or above 12.
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. Sweeteners are perceived by the human sweet taste receptor, hT1R2-hT1R3, which belongs to G protein-coupled receptors, modified by the two histidine residues (i.e. His30 and His60) which participate in the taste-modifying behavior. 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.
As a sweetener
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, lettuce and tomatoes 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.
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. 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". 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. There is informed opinion that the FDA ban could be overturned given sufficient funding for the required safety studies. Miraculin has a novel food status in the European Union. 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).
- doi:10.1016/j.abb.2009.11.008. PMID 19914199. ; 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.
- 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. doi:10.1016/S0021-9258(18)37991-2. PMID 3403544.
- 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.
- 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.
- 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.
- Cudnik DR (27 July 2014). "The miracle berry and miraculin: A review". WordPress. Retrieved 21 September 2019.
- 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. S2CID 24451890.
- Brouwer JN, van der Wel H, Francke A, Henning GJ (October 1968). "Mieraculin, the sweetness-inducing protein from miracle fruit". Nature. 220 (5165): 373–4. Bibcode:1968Natur.220..373B. doi:10.1038/220373a0. PMID 5684879. S2CID 4146207.
- Cagan RH (July 1973). "Chemostimulatory protein: a new type of taste stimulus". Science. 181 (4094): 32–5. Bibcode:1973Sci...181...32C. doi:10.1126/science.181.4094.32. PMID 4714290. S2CID 23665011.
- Giroux EL, Henkin RI (1974). "Purification and some properties of miraculin, a glycoprotein from Synsepalum dulcificum which provokes sweetness and blocks sourness". Journal of Agricultural and Food Chemistry. 22 (4): 595–601. doi:10.1021/jf60194a033. PMID 4840911.
- von Baumgarten R (1975). "[Physiology of smell and taste]". Archives of Oto-Rhino-Laryngology. 210 (1): 43–65. doi:10.1007/bf00453707. PMID 233846. S2CID 40054832.
- 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. doi:10.1016/S0021-9258(18)83477-9. PMID 2708331.
- UniProtKB/Swiss-Prot database entry P13087
- 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.
- 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 (BBA) - Protein Structure and Molecular Enzymology. 1079 (3): 303–7. doi:10.1016/0167-4838(91)90073-9. PMID 1911854.
- 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.
- Mérillon J, et al. (2018). Sweeteners: pharmacology, biotechnology, and applications. p. 169. doi:10.1007/978-3-319-27027-2_17. ISBN 9783319270272. OCLC 1019806685.
- Mangla, B; Kohli, K (2018). "Pharmaceutical and therapeutic potential of miraculin and miracle berry". Tropical Journal of Natural Product Research. 2 (1): 12–17. doi:10.26538/tjnpr/v2i1.3. ISSN 2616-0684.
- 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.
- 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.
- 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. S2CID 9524453.
- 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.
- Slater J (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.
- Cox D (2014-05-29). "The 'Miracle' Berry That Could Replace Sugar". The Atlantic Monthly Group. Retrieved 2018-02-25.
- Gollner AL (31 March 2009). The Fruit Hunters: A Story of Nature, Adventure, Commerce and Obsession. Anchor Canada. ISBN 978-0385662680.
- "Synsepalum dulcificum Import Alert 45-07; Taiwan". US Food and Drug Administration. 5 February 2018. Retrieved 9 February 2018.
- Hieggelke B (2013-04-18). "Sugar Freedom: Chef Homaro Cantu and his Magnificent Miracle Berry Obsession". NewCity Communications Inc. Retrieved 2018-02-25.
- "Novel Food Catalogue". Retrieved 2 July 2013.