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Miraculin is a taste modifier, a
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glyc ...
extracted from the fruit of ''
Synsepalum dulcificum ''Synsepalum dulcificum'' is a plant in the ''Sapotaceae'' family known for its berry that, when eaten, causes sour foods (such as lemons and limes) subsequently consumed to taste sweet. This effect is due to miraculin. Common names for this spe ...
''. 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 Sweetness is a basic taste most commonly perceived when eating foods rich in sugars. Sweet tastes are generally regarded as pleasurable. In addition to sugars like sucrose, many other chemical compounds are sweet, including aldehydes, ketones ...
. When
taste bud Taste buds contain the taste receptor cells, which are also known as gustatory cells. The taste receptors are located around the small structures known as papillae found on the upper surface of the tongue, soft palate, upper esophagus, the che ...
s are exposed to miraculin, the protein binds to the sweetness receptors. This causes normally sour-tasting acidic foods, such as
citrus ''Citrus'' is a genus of flowering trees and shrubs in the rue family, Rutaceae. Plants in the genus produce citrus fruits, including important crops such as oranges, lemons, grapefruits, pomelos, and limes. The genus ''Citrus'' is nativ ...
, to be perceived as sweet. The effect can last for one or two hours.


History

The sweetening properties of ''
Synsepalum dulcificum ''Synsepalum dulcificum'' is a plant in the ''Sapotaceae'' family known for its berry that, when eaten, causes sour foods (such as lemons and limes) subsequently consumed to taste sweet. This effect is due to miraculin. Common names for this spe ...
'' 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 Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glyc ...
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.


Glycoprotein structure

Miraculin was first sequenced in 1989 and was found to be a 24.6 
kilodalton The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
glycoprotein consisting of 191
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s and 13.9% by weight of various sugars.
The sugars consist of a total of 3.4 kDa, composed of a molar ratio of
glucosamine Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of two polysaccharides, chitosan and chitin. Glucosamine is one of the most ...
(31%),
mannose Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ar ...
(30%),
fucose Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) lin ...
(22%),
xylose Xylose ( grc, ξύλον, , "wood") is a sugar first isolated from wood, and named for it. Xylose is classified as a monosaccharide of the aldopentose type, which means that it contains five carbon atoms and includes an aldehyde functional gro ...
(10%), and
galactose Galactose (, '' galacto-'' + ''-ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molec ...
(7%). The
native state In biochemistry, the native state of a protein or nucleic acid is its properly folded and/or assembled form, which is operative and functional. The native state of a biomolecule may possess all four levels of biomolecular structure, with the ...
of miraculin is a
tetramer A tetramer () (''tetra-'', "four" + ''-mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti( ...
consisting of two
dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * Julius Dimer ( ...
s, each held together by a
disulfide In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
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 Kunitz soybean trypsin inhibitor is a type of protein contained in legume seeds which functions as a protease inhibitor. Kunitz-type Soybean Trypsin Inhibitors are usually specific for either trypsin or chymotrypsin. They are thought to protect ...
family.


Sweetness properties

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 bud Taste buds contain the taste receptor cells, which are also known as gustatory cells. The taste receptors are located around the small structures known as papillae found on the upper surface of the tongue, soft palate, upper esophagus, the che ...
s perceive a neutral pH. Sweeteners are perceived by the human sweet taste receptor, hT1R2-hT1R3, which belongs to
G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
s, modified by the two
histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the d ...
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 Xylose ( grc, ξύλον, , "wood") is a sugar first isolated from wood, and named for it. Xylose is classified as a monosaccharide of the aldopentose type, which means that it contains five carbon atoms and includes an aldehyde functional gro ...
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 {{Wiktionary, sweetener A sweetener is a substance added to food or drink to impart the flavor of sweetness, either because it contains a type of sugar, or because it contains a sweet-tasting sugar substitute. Many artificial sweeteners have been ...
in acidic food (e.g. soft drinks). While attempts to express it in
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
and
tobacco plant ''Nicotiana'' () is a genus of herbaceous plants and shrubs in the family Solanaceae, that is indigenous to the Americas, Australia, Southwestern Africa and the South Pacific. Various ''Nicotiana'' species, commonly referred to as tobacco plan ...
s have failed, researchers have succeeded in preparing
genetically modified Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including ...
''
E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Esche ...
'' bacteria,
lettuce Lettuce (''Lactuca sativa'') is an annual plant of the family Asteraceae. It is most often grown as a leaf vegetable, but sometimes for its stem and seeds. Lettuce is most often used for salads, although it is also seen in other kinds of food, ...
and
tomato The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...
es that express miraculin. The scientists' crops resulted in 40
microgram In the metric system, a microgram or microgramme is a unit of mass equal to one millionth () of a gram. The unit symbol is μg according to the International System of Units (SI); the recommended symbol in the United States and United Kingdom whe ...
s of miraculin per
gram The gram (originally gramme; SI unit symbol g) is a unit of mass in the International System of Units (SI) equal to one one thousandth of a kilogram. Originally defined as of 1795 as "the absolute weight of a volume of pure water equal to th ...
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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...
, 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 Taiwan, officially the Republic of China (ROC), is a country in East Asia, at the junction of the East and South China Seas in the northwestern Pacific Ocean, with the People's Republic of China (PRC) to the northwest, Japan to the northeast ...
, 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 A novel food is a type of food that does not have a significant history of consumption or is produced by a method that has not previously been used for food. Designer food Designer food is a type of novel food that has not existed on any regional ...
status in the
European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been ...
. It is approved in
Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
as a safe
food additive Food additives are substances added to food to preserve flavor or enhance taste, appearance, or other sensory qualities. Some additives have been used for centuries as part of an effort to preserve food, for example vinegar (pickling), salt (sal ...
, according to the List of Existing Food Additives published by the Ministry of Health and Welfare (published by
JETRO is an Independent Administrative Institution established by Japan Export Trade Research Organization as a nonprofit corporation in Osaka in February 1952, reorganized under the Ministry of International Trade and Industry (MITI) in 1958 (later the ...
).


See also

*
Brazzein Brazzein is a sweet-tasting protein extracted from the West African fruit of the climbing plant Oubli ('' Pentadiplandra brazzeana'' Baillon). It was first isolated by the University of Wisconsin–Madison in 1994. Brazzein is found in the ex ...
* Curculin *
Monellin Monellin, a sweet protein, was discovered in 1969 in the fruit of the West African shrub known as serendipity berry ('' Dioscoreophyllum cumminsii''); it was first reported as a carbohydrate.GE Inglett, JF May. Serendipity berries - Source of ...
*
Thaumatin Thaumatin (also known as talin) is a low-calorie sweetener and flavor modifier. The protein is often used primarily for its flavor-modifying properties and not exclusively as a sweetener. The thaumatins were first found as a mixture of protein ...
*
Pentadin Pentadin, a sweet-tasting protein, was discovered and isolated in 1989, in the fruit of Oubli ('' Pentadiplandra brazzeana'' ), a climbing shrub growing in some tropical countries of Africa. The fruit has been consumed by the apes and the nativ ...
* Cynarin *
Stevia Stevia () is a natural sweetener and sugar substitute derived from the leaves of the plant species ''Stevia rebaudiana'', native to Paraguay and Brazil. The active compounds are steviol glycosides (mainly stevioside and rebaudioside), which ha ...


References

{{Authority control Taste modifiers Sugar substitutes Food science Biomolecules Chemopreventive agents