Monellin
Encyclopedia
Monellin is a sweet protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 which was discovered in 1969 in the fruit of the West African shrub known as serendipity berry
Serendipity berry
Dioscoreophyllum volkensii , is a tropical dioecious rainforest vine in the family Menispermaceae. It is native throughout most of tropical Africa from Sierra Leone east to Eritrea, and south to Angola and Mozambique. It occurs at low altitudes, from sea level up to 400 m; some authors separate...

 (Dioscoreophyllum cumminsii), it was first reported as a carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...

. The protein was named in 1972 after the Monell Chemical Senses Center
Monell Chemical Senses Center
The Monell Chemical Senses Center is a non-profit independent scientific institute located at the University City Science Center research campus in Philadelphia, Pennsylvania...

 in Philadelphia, U.S.A., where it was isolated and characterized.

Protein composition

So far, five high intensity sweet proteins have been reported: monellin (1969), thaumatin
Thaumatin
Thaumatin is a low-calorie sweetener and flavour modifier. The substance, a natural protein, is often used primarily for its flavour-modifying properties and not exclusively as a sweetener....

 (1972), pentadin
Pentadin
Pentadin, a sweet-tasting protein, was discovered and isolated in 1989, in the fruit of Oubli , a climbing shrub growing in some tropical countries of Africa....

 (1989), mabinlin
Mabinlin
Mabinlins are sweet-tasting proteins extracted from the seed of Mabinlang , a Chinese plant growing in Yunnan province. There are four homologues. Mabinlin-2 was first isolated in 1983 and characterised in 1993, and is the most extensively studied of the four...

 (1983) and brazzein
Brazzein
Brazzein is a sweet-tasting protein extracted from the West African fruit of the climbing plant Oubli . It was first isolated as an enzyme by University of Wisconsin–Madison in 1994....

 (1994).

Monellin's molecular weight is 10.7 kDa
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...

. Monellin is a two noncovalently associated polypeptide chains: an A chain sequence with 44 amino acid residues, and a B chain with 50 residues.

Monellin chain A (44 AA):

REIKGYEYQL YVYASDKLFR ADISEDYKTR GRKLLRFNGP VPPP

Monellin chain B (50 AA):

GEWEIIDIGP FTQNLGKFAV DEENKIGQYG RLTFNKVIRP CMKKTIYEEN

Amino acid sequence of the sweet protein monellin adapted from Swiss-Prot biological database of protein.


Monellin has a secondary structure consisting of five Beta-strands that form an anti-parallel Beta-sheet and a 17-residue Alpha-helix.

In its natural form, monellin is composed of 2 chains (A and B, of 44 and 50 amino acids as shown above), but is unstable at high temperatures or at extremes of pH. In order to enhance its stability, single-chain monellin proteins were created in which the two natural chains are joined via a Gly-Phe dipeptide linker. This modified version of the protein (MNEI) has been studied using NMR and X-ray diffraction.

The image displayed on this page shows the structure of monellin derived from X-ray diffraction at a 1.15 ångström
Ångström
The angstrom or ångström, is a unit of length equal to 1/10,000,000,000 of a meter . Its symbol is the Swedish letter Å....

 resolution. The high resolution used to obtain the structure provided a more detailed look at monellin and its properties than previously possible.

In addition to its secondary structure, four stably bound sulfate ions were located on the monellin protein, three on the concave face of the protein and one on the convex face of the protein. The sulfate ion on the convex face of the protein is of particular interest because it lies adjacent to a patch of positive surface potential, which may be important in electrostatic interactions with the negative T1R2-T1R3 sweet taste protein receptor.

Sweetness properties

Monellin is perceived as sweet by humans and some Old World primates, but is not preferred by other mammals. The relative sweetness of monellin varies from 800 to 2000 times sweeter than sucrose, depending on the sweet reference it is assessed against. It is reported to be 1500-2000 times sweeter than a 7% sucrose solution on a weight basis<
and 800 times sweeter than sucrose when compared with a 5% sucrose solution on a weight basis.
Monellin has a slow onset of sweetness and lingering aftertaste. Like miraculin
Miraculin
Miraculin is a natural sugar substitute, a glycoprotein extracted from the fruit of Synsepalum dulcificum. The berry, which contains active polyphenols, was first documented by explorer Chevalier des Marchais, who searched for many different fruits during a 1725 excursion to its native West...

, monellin's sweetness is pH dependent; the protein is tasteless below pH 2 and above pH 9.
Blending the sweet protein with bulk and/or intense sweeteners reduces the persistent sweetness and shows a synergistic sweet effect.

Heat over 50°C at low pH denatures monellin proteins causing a loss of the sweetness.

As a sweetener

Monellin can be useful for sweetening
Sugar substitute
A sugar substitute is a food additive that duplicates the effect of sugar in taste, usually with less food energy. Some sugar substitutes are natural and some are synthetic. Those that are not natural are, in general, called artificial sweeteners....

 some foods and drinks as it is a protein readily soluble in water due to its hydrophilic properties. However it may have limited application because it denatures under high temperature conditions which makes it unsuitable for processed food. It may be relevant as noncarbohydrate tabletop sweetener,especially for individuals such as diabetics who must control their sugar intake.

In addition, monellin is costly to extract from the fruit and the plant is difficult to grow. Alternative production such as chemical synthesis and expression in micro-organisms are being investigated. For instance, monellin has been expressed successfully in yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...

 (Candida utilis) and synthesised by solid-phase method. The synthetic monellin produce by yeast was found to be 4000 times sweeter than sucrose when compared to 0.6% sugar solution.

Legal issues are the main barrier in widespread use as a sweetener as Monellin has no legal status in the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...

 or the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

. However, it is approved in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

 as a harmless additive
Food additive
Food additives are substances added to food to preserve flavor or enhance its taste and appearance.Some additives have been used for centuries; for example, preserving food by pickling , salting, as with bacon, preserving sweets or using sulfur dioxide as in some wines...

, according to the List of Existing Food Additives issued by the Ministry of Health and Welfare (published in English by JETRO).
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