On May 17, the National Health Commission issued a notice on the acceptance of new food raw materials, including the "longevity Vitamin" - ergothionein. The release of this announcement indicates that ergothione, as a cosmetic and food homologous ingredient, may usher in new development possibilities in the field of oral anti-aging. Ergothioneine is a high-potential ingredient in skin care and a hot ingredient in synthetic biology. According to Market Watch, the market size of ergothioneine is expected to reach $171.9 million by 2028, with a compound annual growth rate of 36.2% during the forecast period 2022-2028. 01
Ergothioneine: Super antioxidant C position
Ergothioneine (EGT) is a naturally occurring amino acid, and in 1909, Charles Tanret, while studying the ergot fungus that destroys rye grains, isolated a unique crystalline sulfur-containing compound, which was subsequently named ergothioneine. In 1911, Barger and Ewins determined its structure and found that ergothionein was a derivative of histidine betaine.
Ergothionein has tautomers in both mercaptan and thioketone forms, and the thioketone tautomers dominate at physiological pH, which makes ergothionein exceptionally strong antioxidant properties. According to Huaxi Biological data, the DPPH radical scavenging ability of ergothioneine Bioyouth™-EGT is 14 times that of glutathione and 30 times that of Coenzyme Q10 at the same concentration, which belongs to the well-deserved super antioxidant C position. . Studies have shown that the antioxidant mechanism of ergothionein is multi-fold, and it can clear active oxygen in the body and inhibit oxidative stress through various mechanisms, thus playing an antioxidant role [1]. 1, direct removal of free radicals: ergothione can directly react with free radicals to remove active oxygen species in the body, such as hydroxyl free radicals, superoxide free radicals, hydrogen peroxide, etc. This direct clearance mechanism is the basis of the antioxidant effects of ergothionein. 2, metal ion chelation: ergothione can form a stable chelate with transition metal ions (such as copper ions) in the body, thereby preventing metal ions from catalyzing oxidative stress reactions. 3, activation of antioxidant enzymes: ergothioneine can activate antioxidant enzymes, such as superoxide dismutase, glutathione reductase and catalase, the activation of these enzymes helps to remove reactive oxygen species in the body. Besides. It can activate the Nrf2/ARE antioxidant pathway and thus up-regulate the expression of various antioxidant enzymes. 4, inhibit oxidase activity: ergothioneine can inhibit the activity of oxidase, such as lipid peroxidase and xanthine oxidase, thereby reducing the production of reactive oxygen species. 5, protect DNA: ergothione can protect DNA from oxidative stress damage, thereby preventing gene mutation and cell death, and can also regulate the expression of genes related to cell cycle and apoptosis, affecting the oxidative stress damage of cells. 02
Eye care, anti-aging, versatility of ergothione
Based on the characteristics of strong antioxidant, high stability and non-toxicity, ergothione has been gradually confirmed by more and more studies to have a positive impact on human health. Unlike polyphenols, ergothionein is excreted very slowly in the body, so it can be highly retained in the body tissues and red blood cells of people and other animals to fully play its role.
1) Eye protection
Ergothione is present in high concentrations in eye tissues, including the lens, retina, cornea, and retinal pigment epithelium, and may help protect the eye by removing chronic reactive oxygen species (ROS), reducing intracellular ROS production, and inhibiting oxidation-induced epithelial mesenchymal transformation (EMT). The L-ergothione ingredient MitoPrime from NNB Nutrition can help improve age-related visual degeneration. MitoPrime is produced through a patented natural fermentation process and can be made into nutritional beverages, foods, beverages, sugars, capsules, tablets, powders, etc. 2) Skin anti-aging
Skin aging is a multifactorial process, including epidermal aging due to UV radiation, dermal aging due to collagen loss, and submuscular inflammation due to apoptosis. Ergothionein, through its unique biological activity, has demonstrated significant anti-aging effects on different skin levels: A. Anti-UV protection of the skin layer: Ergothionein acts as a potent antioxidant and plays an important role in protecting against skin damage from UVA and UVB radiation. It protects skin cells from DNA breakage and mutation and mitochondrial damage by alleviating the inflammatory response triggered by UV radiation [2]. B. Collagen maintenance of dermis: In the dermis, ergothione enhances collagen synthesis and reduces collagen loss after UV exposure. Studies have shown that ergothione can significantly improve the activity of fibroblasts, reduce the activity of matrix metalloproteinase (MMP-1) and enhance the production of type I collagen [3], thus inhibiting UV-induced photoaging and reducing the damage of collagen by 72.9%[4]. C. Cell recharge and repair in the submuscular layer: In the basal layer of the skin, ergothione has a positive effect on cell energy metabolism, prolongs cell life by increasing telomerase activity, and promotes the rapid renewal and repair of skin tissue [5]. In view of the potential of ergothione in skin care, SUPER-SYN proposed the concept of "muscle bottom charging, layered anti-aging" to provide comprehensive support for skin health. 3) Protect brain health & improve cognitive function
There is an association between ergothioneine levels and cognitive function and/or neurodegeneration in humans, and a randomized, placebo-controlled, double-blind, parallel group study in humans found that continuous oral administration of ergothionein-containing mushroom extract tablets for 12 weeks enhanced cognitive function compared to placebo groups. Since 2020, the Japanese market has begun to launch functional labeled foods containing ergothionein, focusing on improving the memory function of the elderly. The ergothionein supplement launched by LS Corporation is a product for the memory decline of middle-aged and elderly people. Studies have shown that ergothioneine can pair glutathione to reduce iron-myoglobin, chelate transition metal iron to remove reactive oxygen species and active nitrogen (ROS/RNS) and free radicals produced during ischemia-reperfusion, regulate pro-inflammatory cytokines such as IL-1β and TNF-α, and ultimately prevent myocardial injury [6]. These results indicate that the inhibitory inflammatory pathway of ergothionein is the main mechanism of alleviating various cardiovascular diseases. 5) Liver protection Bedirli et al. [7] administered 70 mg/kg ergothione to rats with liver ischemia-reperfusion by intragastric administration, and found that HSP70 content in liver was increased after administration, liver injury was improved, and the survival rate of rats was significantly increased. 6) Improve intestinal health With the change of people's eating habits and the increase of life pressure, more and more people are facing intestinal health problems, and the incidence of inflammatory bowel disease is rising. Studies have found that ergothione extracted from oyster mushroom can down-regulate the expression of pro-inflammatory factors, inhibit the TLR4/MyD88/NF-κB signaling pathway, and significantly alleviate the colon length shortening and colon pathological injury induced by sodium glucan sulfate in mice [8]. 7) Sleep improvement Ergothionein can penetrate the blood-brain barrier through various biological mechanisms, inhibit the formation of peroxynitrite and nitrification of tyrosine residues, and impede the apoptosis of brain nerve cells [9], thus reducing stress, relieving depression, and improving sleep difficulties [10]. SUPER SYN's deep sleep emergency tablet combines GABA, L-theanine, casein peptide and other ingredients to solve the problems of "difficulty falling asleep (long sleep latency)," "difficulty in maintaining sleep (frequent awakenings or night awakenings)," and "poor sleep quality (non-restorative sleep)" and repair the body's functions during deep sleep. 03
Synthetic biology to achieve "ergothionein freedom"
At first, ergothionein was mainly extracted from mushrooms and ergot, this natural source was low in content, and the purification process was time-consuming and costly, with a kilogram of ergothionein costing close to $1 million. Later, the American raw material company Barnet used the chemical synthesis route to produce ergothione, which was affected by the cost, and its market price was converted into a pure powder of about 7,000 yuan /g, which can be seen that even if the process progress, the price of ergothione is still very high. However, with the rapid development of synthetic biology, ergothioneine can eventually achieve "price freedom".
According to the summary of Li Liang et al., there are three kinds of biosynthesis methods [11] : (1) The use of natural microorganisms with the ability to synthesize ergothione directly for liquid deep fermentation, such as edible mushroom; (2) ergothionein was synthesized by biotransformation using L-His, L-Cys and L-Met as substrates by expressing ergothionein synthases in plasmids; (3) The engineering strain of ergothionein was used for fermentation, synthetic biology technology was introduced into the ergothionein synthesis module, and the key enzymes in the synthetic metabolic pathway of ergothionein synthase and precursor amino acids were reasonably reformed to achieve an efficient combination, and metabolic engineering and fermentation engineering were combined to regulate the metabolic flux of precursor substances and fermentation culture conditions. Biosynthesis is expected to produce ergothionein efficiently. Enterprises, universities and research institutes have begun to study how to efficiently prepare ergothioneine through synthetic biology, which can improve the yield and reduce the cost while improving the purity. Japanese research has shown that using engineered microbes for fermentation could potentially reduce the cost of ergothionein production by 99%. Blue California was the first company to produce L-ergothioneine by fermentation, launching the ErgoActive ingredient in 2015 as an alternative to chemical synthesis and mushroom extraction of ergothioneine. According to the official website of Huaxi Biology, the current ergothione produced by the company includes ergothione extract (Bioyouth™-EGT), Bioyouth™-EGT Pro Super live ergothione, and Bioyouth™-EGT Pure super pure ergothione. Bioyouth™-EGT is prepared by the joint fermentation of the mycelium of hericium mushroom and mushroom. Zhongkosinyang has completed the evaluation of tens of thousands of ergothionein synthases, established the maximum carbon nitrogen sulfur load metabolic model, combined with the innovative total synthesis path of green low-sugar fermentation technology, to increase the proportion of non-grain biomass carbon sources in fermentation, and help low-carbon manufacturing and carbon cycle. At present, the scale of single tank fermentation has reached 100 tons, achieving more than 99% high purity and strong stability. The appearance is upgraded from yellow powder to white flash crystal, uniform particle size distribution, stable quality, not easy to carry impurities, nor easy to absorb moisture, and obtained 3 purification process patents. Shanghai ergothionein Biotechnology Group adopts chemical enzyme coupling method to synthesize ergothionein, which realizes the efficient production of ergothionein, which is the first in the industry. The purity of ergothione is as high as 99.9%, the rotation [α]D is ≥(+)124°, and the product form is rod-like transparent crystal. Only with advanced biosynthesis technology, Sanbioli achieves mass production and purification processing capacity of 20 tons fermenter, monthly production capacity of 3 tons, cost straight down 90%, cGMP pharmaceutical standard platform production, product purity up to 99.99%. At the same time, only Sanbio applied the self-developed ergothione to its beauty skin care products and oral health care brands, such as GeneIII ergothione oral capsule, one capsule contains 25mg ergothione, and 2 capsules ≈ supplement 1 jin of fresh ganoderma lucidum. Image source: Lu Long, a researcher at the Shanghai Institute of Organic Chemistry of the Chinese Academy of Sciences, led his team to efficiently and directionally optimize EGT1 and EGT2, two key enzymes in the ergothione biosynthesis pathway, through high-throughput enzyme directed evolution technology, which is said to achieve a yield of more than 80% and a purity of more than 99.9%. And the price is only 1/3 of the market price. 04
The road to compliance of ergothioneine at home and abroad
1) China In 2014, ergothione was officially included in the "Catalogue of Used Cosmetic Raw Materials" by the State Medical Products Administration. With its excellent antioxidant properties, ergothione has gradually become a major ingredient in the skin care industry. At present, ergothione is applying as a new food raw material, indicating that it will achieve cross-industry application expansion in the field of domestic food and functional food. 2) EU In July 2017, the EU approved L-ergothione as a new food ingredient that can be used in Dietary supplements, 30 mg per day for the general population and 20 mg per day for children over 3 years of age, and cannot be used in pregnant and lactating women. In 2018, the European Union expanded the use of L-ergothioneine, in addition to dietary supplements, can also be applied in beverages, cereal bars and other common foods. 3) In the United States, in August 2019, ergothioneine passed the GRAS certification of the United States FDA and can be used in common foods. 4) Japan From 2020, the Japanese market began to introduce functional expression foods containing ergothionein, focusing on improving memory function of the elderly. 5) Canada Health Canada approves ergothioneine as a medicinal/non-medicinal natural health product, and in non-medicinal cases, as a preservative, antioxidant, skin conditioner.
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2024-05-24
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