INTRODUCTION
Miraculin is a glycoprotein extracted from the fruit of Synsepalum dulcificum known to turn every sour-like taste into a sweet sensation, because of that its berries are called Miracle Fruit. The effect averagely run out in 30-60 minutes.
The plant was discovered by Chevalier des Marchais in 1725 during an excursion in West Africa, where it was used to sweeten palm wine.
An attempt was made in the 70’s to commercialize it as a low-carb food additive without any success.
Miraculin - Wikipedia
Synsepalum dulcificum - Wikipedia
MOLECULE’S INTERACTION
Miraculin (MCL) itself is not perceived as a sweet substance, though it does bind with G protein-coupled heterodimeric receptors such T1R2 and T1R3 (Molecular mechanisms of the action of miraculin, a taste-modifying protein - 2013), the same kind used by sweet-taste cellular pathway. As a matter of fact, the connection between the protein and the receptors does not trigger any cellular response until the pH inside the mouth becomes lower than 7.5. In fact the increased concentration of protons changes the structure of the molecule causing it to interact with those receptors making them more prone to the activation.
Structural insights into the aggregation behavior of Murraya koenigii miraculin-like protein below pH 7.5. - 2013
In particular analysis of symmetry-related molecular interfaces shows how the intermolecular contacts tend to shorten as the pH decreases, especially the ones related to the Tryptophan103 contained in the binding site.
This explains how miraculin has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 30 minutes each time we taste a sour solution.
Empiric observations suggest that the increased acidity of the environment is the key for miraculin effect: the more acid the mouth becomes, the sweeter anything would eventually taste.
However, the miraculin administration will not affect bitter taste substances, for they lack protons to activate the molecule with.
Moreover, a trial conduct with the administration of aspartame and other sweetener substances shows that as long as MCL remains in a neutral/basic environment it will not activate the receptors, as previously mentioned, but it will also prevent other sweetener substances from doing it. It seems likely that MCL binds hT1R2-hT1R3 as an antagonist at neutral pH and functionally changes into an agonist at acidic pH.
Human sweet taste receptor mediates acid-induced sweetness of miraculin - 2011
On the other hand, the enhanced sensation felt due the administration of MCL and another sweetener shows that the molecule probably work as a receptor stabilizer, keeping the dimer in an active form, when T1R2 and T1R3 are eventually more prone to be activated by another ligand (aspartame, sorbitol, sucrose, etc.).
CLINICAL RELEVANCE
Sweet proteins have the potential to substitute the sugars, by acting as natural, good and low calorie sweeteners. Patients affected with diabetes could really benefit by MCL administration, since, being a peptide, miraculin does not trigger a demand for insulin. In conclusion, MCL could be considered a valid adjuvant for substances commonly used as a sweet additive, in sour food or beverages.
Miracle fruit improves sweetness of a low-calorie dessert without promoting subsequent energy compensation - 2011
Another application of MCL would be the one concerning obese people. It provides with a fine substitute for sorbitol, xylitol and aspartame, used as zero-cal sweeteners, for they first two have known laxative effects while the last one has a controversial history of toxicity brought by his methanol content.
Identification of novel sweet protein for nutritional applications - 2011
Miraculin has also been used in patients undergoing cancer’s chemotherapy treatment. For it is mildly common for these people to experience a characteristic metal taste in their mouth. A Pilot study was designed to determine whether consumption of the Miracle Fruit supplement would improve chemotherapy-associated taste changes, thereby improving the taste of food and ultimately leading to better nutrition. Half of the participants were given a two-week supply of the supplement and the other half were given a two-week supply of a placebo. After two weeks, the supplement group received a two-week supply of the placebo and the placebo group received a two-week supply of the supplement. Participants recorded food and drink intake in daily food dairies and rated taste changes with each food as better, worse, or no change. All study participants reported positive taste changes with the supplement.
Pilot study of Miracle Fruit to improve food palatability for patients receiving chemotherapy - 2012
USE’S LIMITATIONS
Anybody would ask himself, at this point, why Miraculin has not found, yet, a way of entering into our drug market. 
The thing of the matter is that, nowadays, MCL is still too expensive and still lacks a reasonably high number of well conducted studies. Moreover this protein has shown a lack of stability under heat around 100°C, giving that, it is not possible to cook it. By the way, MCL is widely used in Japan, where dedicated cafés are serving low-cal food with a miracle fruit on the side.
Super Lettuce Turns Sour Sweet - 2006
Now, that being said, one may easily ask himself about the indirect dangers implied in the intaking of the MCL. Since Miraculin change how our body interacts with sour substances for several minutes, it may enhance the risk of poisoning. A patient under the influence of Miraculin may not recognize poison, drugs and acids, therefore its use must be diligent and aware.
