Antioxidant "great devil" - ergothioneine

L-Ergothioneine (EGT) is a natural antioxidant that protects the proteins of DNA from oxidative damage; At the same time, as a rare sulfur-containing amino acid (L-mercaptohistidine trimethylendolide), it is a natural cell protectant and antioxidant in the human body, with anti-photoaging and antioxidant effects. The molecular structure is shown below:

Distribution Range

Ergothionein is distributed in some tissues and organs of mammals, mainly in red blood cells (about 1 to 2 mmol.L) and semen of some animals, although there is no experimental research that animals can synthesize the substance, but there is certainly a way to absorb and retain ergothionein in animal cells. For carnivores, ergothioneine in animal tissues can supply dietary needs. Melville.D.B and Eich.S [1] found that ergothionein also exists in cereal plants. Subsequent studies by Melville.D.B., Genghof.D.S., et al., showed that ergothioneine is a common component of many microbial cells and can be synthesized in several fungi, but not in bacteria. The precursor histidine trimethylendine (hercynine), which is necessary for the synthesis of ergothionein, can be produced in edible fungi such as porcini, mushroom and pilosa. It can also produce rare amino acids such as ergothione.

Preparation Method

There are three methods of preparation of ergothionein: chemical synthesis, extraction and biological fermentation synthesis.

The chemical synthesis of L-ergothione is very difficult, and several synthetic methods do not reach the expected yield due to partial or full racemization. The difficulty of synthesis is that it is difficult to prepare the raw material 2-mercaptoimidazole, and the acidity of the alpha carbon will make the reaction very easy to racemize. OXIS International was the first company to develop an efficient and commercially available method for the synthesis of ergothioneine [2], which was patented in 1995 by introducing sulfhydryl groups into imidazole rings. However, because the safety of chemical synthetic products is difficult to be guaranteed, the synthetic raw materials are expensive, the synthetic cost is high, and the price of products is high, which limits the application of ergothionein.

The natural biological extraction method is to extract ergothionein from the fruit bodies of edible fungi, pig blood, animal tissues, ergothionein and grains, but the content of ergothionein in the above raw materials is still very low, and there are many impurities in the raw materials, drug residues, high extraction cost, which limits the application of ergothionein and is not suitable for industrialization.

Biosynthesis of ergothionein by deep fermentation technology of mushroom mycelium is the mainstream direction of low-cost large-scale production of ergothionein, which can effectively improve the yield of ergothionein and reduce the production cost through metabolic regulation and other fermentation process control methods. More importantly, it can ensure the safety of products and broaden the application space of ergothionein.

Biological Function

1. Antioxidant effect: Ergothionein is a natural amino acid that comes from plants and can be accumulated in animals. Studies have proved that it has the function of antioxidant. It can effectively remove -OH, chelate iron and copper ions, and prevent H2O2 from forming -OH under the action of iron or copper ions. It also inhibits the oxidation of copper-dependent oxygenated hemoglobin and the peroxidation of arachidonic acid when myoglobin (or hemoglobin) is mixed with H2O2. Ergothionein also strongly removes hypochlorous acid, thereby preventing the inactivation of A1-antiprotease. However, it cannot inhibit the peroxidation of lipid particles in the presence of iron ions. AKanmu D et al. showed that a certain concentration of ergothione in the body can act as an antioxidant.

2. Cell protection: Ergothioneine is a powerful hypochlorous acid scavinger (HOCl), and while many compounds react with hypochlorous acid, few react as quickly as ergothioneine. a1 - antiprotease inhibitors (apis), such as elastase, are particularly sensitive to hypochlorous acid, and physiological concentrations of ergothione are very effective in protecting apis against hypochlorous acid-induced inactivation, since neutrophils are the main source of hypochlorous acid in the body. One of the roles of ergothionein is to protect red blood cells from neutrophils that come from sites of normal function or pathological inflammation.

3. Anti-inflammatory effect: Peroxynitrite is the endogenous formation of NO and superoxide in limited diffusion reaction, and is a strong oxidant related to the pathophysiology of inflammation, such as ischemia reperfusion injury, atherosclerosis, acute pneumonia and sepsis. Ergothione can inhibit the oxidation of amino acids mediated by peroxynitroso anions, such as the nitration of tyrosine, thus providing a feasible treatment for inflammation.

Usage

For the significant and unique biological functions of ergot sulfur substances, scholars in various countries have long launched research on its application, although it needs to be further in-depth, but it has a good enlightening effect on its application in various fields. Ergothionein has a wide range of applications and market prospects in organ transplantation, cell preservation, medicine, food and beverage, functional food, animal feed, cosmetics and biotechnology.

1. Used as a unique antioxidant: ergothioneine is a highly protective, non-toxic natural antioxidant that is not easily oxidized in water, which allows their concentration in some tissues to reach mmol and activates the cell's natural antioxidant defense system. Among the many antioxidants, ergothione is particularly unique, because ergothione can chelate heavy metal ions, which can make the red blood cells in the body free from free radical damage.

2. For organ transplantation: The storage capacity and preservation time of existing tissues play a decisive role in the success of organ transplantation surgery. The most commonly used antioxidant for organ transplant preservation is glutathione, which is easily oxidized when exposed to the environment, even when refrigerated or in a liquid environment, its antioxidant capacity is greatly reduced, causing cell toxicity and inflammation, inducing hydrolysis of tissue proteins. Because ergothione is stable in aqueous solution and can chelate heavy metal ions as an antioxidant, it can be used as a substitute for glutathione in the field of organ protection to better protect transplanted organs.

3. Added to cosmetics as a skin protective agent: ultraviolet UVA in the sun can penetrate into the dermis of human skin, affecting the growth of epidermal cells, making surface cells die of old age, causing premature aging of the skin, and ultraviolet UVB is easy to lead to skin cancer. Ergothione can minimize the formation of reactive oxygen species and protect cells from radiation damage, so ergothione can be used as a skin protective agent added to some cosmetics for the development of outdoor skin care products and protective cosmetics.

4. Application in ophthalmology: In recent years, studies have found that ergothione plays a key role in protecting the eye, so many researchers hope to develop an ophthalmic product to promote the development of eye treatment surgery. Ophthalmic surgery is usually performed locally, and the water solubility and stability of ergothioneine provide feasibility for this kind of surgery, which has great application value.

Cite: [1] 1. Melville.D.B,Eich. S. The occurrence of ergothioneine in plante meterial[J]. J Biol Chem,1956,218(2):647-651

[2] 2. XU J.and YADAN J.C.，A new and convenient synthesis of imidazole-2-thiones from Imidazole.Synlett，1995.3 ：239-241.

[3] 3. H.Heath,Biochem,J.,54(1953)689