BONE
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2025
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IF 3.6
Zhen Guo,Yiwen Huang,Xiaowei Wang,Yi Han,Ang Li,Yiyang Qu,Lin Chen,Meihang Du,Yiming Zhang,Yuanzhi Xu
The accumulation of reactive oxygen species (ROS) within cells regulates the formation and function of osteoclasts, which is crucial therapeutic target for the treatment of osteoporosis. Ergothioneine (EGT) is a rare amino acid with strong antioxidant and anti-inflammatory properties. However, its application on osteoporosis has not been reported. In this study, we investigated the effects of EGT on osteoclastogenesis in vitro and in ovariectomized (OVX) mice. The results revealed that EGT could suppress RANKL-induced podosome belt formation and osteoclast development in vitro, while reducing intracellular ROS levels by upregulating key antioxidant enzymes, including HO-1 and Catalase. EGT was also found to downregulate the expression of critical osteoclast-specific proteins such as Trap, c-Fos, and Ctsk through attenuation of MAPK signaling. The potential of EGT to protect against trabecular bone loss in OVX mice was further demonstrated by micro-CT imaging, possibly by reducing osteoclast numbers shown by histological outcomes. These findings together highlighted the potential value of EGT as a novel tool for treating osteoporosis through its ability to suppress osteoclastogenesis and mitigate the accumulation of intracellular ROS.
研究领域:
医学
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细胞生物学
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PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Shuzhen Chen,Wenjing Lin,Yan Zhang,Fan Cai,Wei Lin,Jianbin Xiao,Xingtong Chen,Qin Li,Huaidong Zhang,Mingliang Zhang,Li Li
Ergothioneine (EGT), a histidine derivative with diverse physiological functions, has broad applications in food, cosmetics, and pharmaceuticals. Fermentative production of EGT using recombinant Saccharomyces cerevisiae is widely considered the most cost-effective and direct method. However, no previous studies have explored improving EGT production in S. cerevisiae through protein fusion technology. In this study, we present the first successful construction of a fungal EGT biosynthesis pathway in S. cerevisiae , coupled with enzyme fusion techniques and optimization of gene copy integration. The engineered strain, SZA011, achieved a record EGT production of 122.5 mg/L under optimized shake flask fermentation conditions. Moreover, in a 10 L fed-batch fermentation system, SZA011 produced 626.24 mg/L of EGT. This study introduces a novel strategy for enhancing microbial EGT generation through protein and genetic engineering, potentially enabling industrial applications.
研究领域:
生物工程
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微生物学
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高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2025
·
IF 8.2
Hailin Wang,Yueying Wang,Xin Li,Jiayang Ma,Zhiqi Hu,Qian Qu,Yong Miao
Hair graying and loss are significant indicators of aging, and oxidative stress plays an essential role in this progression. Ergothioneine (EGT), potent antioxidant from edible fungi and certain prokaryotes, regulates the antioxidant defense system. However, its anti-aging effects on hair follicles (HFs) are remain obscure. We used dermal papilla cells (DPCs) co-culture system, HFs organ culture system, aged mice and H 2 O 2 -induced gray hair mice to explore the antioxidative functions and mechanisms of EGT on HFs. Research demonstrated that EGT mitigated H 2 O 2 -induced DPCs damage, reduced the secretion of inflammatory factors (IL-6, IL-1β, and TNF-α) and enhanced the production of pigmentation promoting factors (SCF and SDF1) through the SIRT1/Nrf2 pathway in DPCs. In vitro experiments of co-culture system indicated that EGT-treated DPCs remarkably alleviated oxidative damages and promoted cell proliferation in A-375 and HaCaT. Furthermore, it increased tyrosinase activity, melanin content and the expression of key melanin synthesis genes in A-375. Meanwhile, it promoted the expression of K19 and K14 in HaCaT. In vivo experiments revealed that EGT exhibited excellent effects on reducing pigmentation disfunction and hair loss in aged mice and H 2 O 2 -induced gray hair mice. In the HFs organ culture, the EGT promoted hair growth and pigmentation via SIRT1/Nrf2 partly. Our research indicated that EGT had potent antioxidant and anti-aging functions for HFs. This not only provided new applications for EGT but also opened up new therapeutic avenues for hair aging.
研究领域:
细胞生物学
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医学
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分子生物学
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PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2025
·Vol. 109
·期 1
·1-11
·
IF 4.3
Wang Lihong,Tian Xueqin,Xue Pinghong,Deng Yunhong,Gao Rui,Hu Zhihong
Ergothioneine (EGT) is a rare amino acid with potent antioxidant and anti-inflammatory properties, with a wide range of applications in food, cosmetics, and medicine. In the present study, Aspergillus oryzae , a common edible fungus, was engineered as an optimal host for EGT production. Moreover, two endogenous genes involved in EGT biosynthesis were characterized. The homolog AoEgt1 was shown to be localized in the vacuoles, whereas the homolog AoEgt2 was found in the peroxisomes. Overexpression of EGT biosynthetic genes from different organisms enhanced EGT production, yielding 15.17 mg EGT/g of dry weight. Using glucose as the carbon source and supplementing methionine (Met) as a precursor further increased EGT production to 20.03 mg EGT/g of dry weight, constituting an eight-fold increase compared to the wild-type strain. This study discusses the successful construction of a high-yielding A. oryzae strain for EGT biosynthesis, providing a novel strategy for efficient EGT synthesis. Key points • Two newly described homologs, AoEgt1 and AoEgt2, were identified in A. oryzae. • AoEgt1 and AoEgt2 were found to contribute to EGT biosynthesis. • EGT production was significantly increased by overexpression of Egt1 and Egt2. • Glucose and Met supplementation in the medium increased EGT production.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Yating Gu,Shujingwen Wang,Bo Si,Chun Chang,Hao Ma,Yonglin Lu,Lishuang Lv
Acrolein (ACR) present in vivo and in vitro can damage proteins and DNA, linking it to various chronic diseases. In this paper, ergothioneine (EGT), abundant in edible mushrooms, has been studied for its ability to trap ACR and its reaction pathway with ACR at high temperatures using ultraperformance liquid chromatography–mass spectrometry (UPLC–MS/MS). We synthesized the adducts (EGT-ACR-1 and EGT-ACR-2), elucidating their structure and reaction site through HRMS and nuclear magnetic resonance. Subsequently, we proved the synergistic trapping effect on ACR of EGT when combined with γ-aminobutyric (GABA) and disodium 5′-guanylate (GMP) in binary or ternary employing the Chou–Talalay methods. Quantitative analysis of the ACR adducts revealed that GABA and GMP enhanced EGT’s ability to form additional ACR adducts. Moreover, Boletus eduli and Volvariella volvacea, as the carriers of EGT, GABA, and GMP, show a marked effect on trapping ACR generated during the baking of cookies/cakes. Our finding suggested that EGT, whether as a standalone compound or derived from mushrooms, could act as a potential ACR capturer (including single and multiple uses) in baked food.
研究领域:
生物化学
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食品科学
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医学
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PubMed
高影响因子
Biotechnology Journal
·
2024
·Vol. 19
·期 11
·e202400527
·
IF 3.2
Chaoqun Tang,Lu Zhang,Junyi Wang,Congjia Zou,Yalin Zhang,Jifeng Yuan
Saccharomyces boulardii , as a probiotic yeast, has shown great potential in regulating gut health and treating gastrointestinal diseases. Due to its unique antimicrobial and immune-regulating functions, it has become a significant subject of research in the field of probiotics. In this study, we aim to enhance the antioxidant properties of S. boulardii by producing l -ergothioneine (EGT). We first constructed a double knockout of ura3 and trp1 gene in S. boulardii to facilitate plasmid-based expressions. To further enable effective genome editing of S. boulardii , we implemented the PiggyBac system to transpose the heterologous gene expression cassettes into the chromosomes of S. boulardii . By using enhanced green fluorescent protein (EGFP) as the reporter gene, we achieved random chromosomal integration of EGFP expression cassette. By using PiggyBac transposon system, a great variety of EGT-producing strains was obtained, which is not possible for the conventional single target genome editing, and one best isolated top producer reached 17.50 mg/L EGT after 120 h cultivation. In summary, we have applied the PiggyBac transposon system to S. boulardii for the first time for genetic engineering. The engineered probiotic yeast S. boulardii has been endowed with new antioxidant properties and produces EGT. It has potential applications in developing novel therapeutics and dietary supplements for the prevention and treatment of gastrointestinal disorders.
研究领域:
微生物学
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遗传工程
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营养学
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PubMed
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Cell Host & Microbe
·
2026
·
IF 23.2
Mingxuan Zheng,Hanrong Yan,Wenting Hao,Huimei An,Xi Chen,Qingyuan Wu,Xing Ge,Huaiyu Ye,Menglu Zhou,Guorong Zhou,Xiaoying Yang,Minmin Hu,Peng Zhang,Wei Pan,Renxian Tang,Kuiyang Zheng,Xu-Feng Huang,Yinghua Yu
Chronic antipsychotic use is associated with neuronal damage and cognitive impairment, with the gut microbiome increasingly implicated. However, the specific microbial metabolites and mechanisms involved remain unknown. Here, we demonstrate that chronic olanzapine treatment induces gut microbial dysbiosis, compromises intestinal barrier integrity, and causes cognitive deficits in mice. Multi-omics analyses reveal profound depletion of the microbiota-associated metabolite ergothioneine in blood and brain, a finding validated in the blood of olanzapine-treated patients and risperidone- and clozapine-treated mice. This deficiency correlates with a loss of ergothioneine-producing bacteria (Cyanobacteria and subordinate taxa). Fecal microbiota transplantation from olanzapine-treated mice confers cognitive impairment, while ergothioneine supplementation mitigates it. Mechanistically, ergothioneine attenuates hippocampal oxidative stress and inhibits the redox-sensitive phosphatase protein tyrosine phosphatase 1B (PTP1B). Furthermore, hippocampal neuronal-specific PTP1B deletion abolishes olanzapine-induced synaptic and cognitive deficits. Our findings identify depletion of microbiota-derived ergothioneine as a mechanism underlying antipsychotic-induced cognitive impairment, highlighting therapeutic strategies to mitigate this side effect.
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PubMed
高影响因子
CURRENT EYE RESEARCH
·
2026
·
IF 1.7
Rujun He,Wei Ding,Juan Cao,Cong Guo,Xu Li,Guohua Xiao
Purpose To evaluate ergothioneine (EGT), a naturally occurring amino acid and endogenous antioxidant, as a novel therapeutic agent for oxidative stress-related ocular diseases. This evaluation specifically aimed to address the challenge of targeted ocular delivery by assessing EGT’s antioxidant potency, stability, ocular tolerance, and crucially, its ability to reach the posterior segment (fundus) via topical administration.Methods This study evaluated EGT as a novel ocular antioxidant by examining its radical scavenging capacity (DPPH assay compared to glutathione, astaxanthin, and coenzyme Q10), stability (at 40 °C/75% relative humidity for six months using HPLC), ocular tolerance (using a New Zealand rabbit model), and fundus delivery efficiency (topical D9-EGT eye drops quantified by LC-MS/MS).Results EGT demonstrated significantly superior radical scavenging activity, exhibiting 6.4-fold and 46-fold higher rates than glutathione and coenzyme Q10, respectively, at 50 ppm. It also showed excellent stability, retaining over 97% of its initial concentration after six months, and caused no ocular irritation at any tested concentration (score 0). Importantly, topical administration of EGT resulted in effective fundus delivery, with peak concentrations reached at 0.5 h post-application (1181 ± 56 ng/g), confirming successful penetration through corneal and scleral barriers. These findings establish EGT as a potent, multi-mechanistic antioxidant characterized by high stability, ocular safety, and exceptional posterior segment penetrance via noninvasive eye drops.Conclusion These findings establish EGT as a potent, multi-mechanistic antioxidant characterized by high stability, ocular safety, and exceptional posterior segment penetrance via noninvasive eye drops. By overcoming key delivery limitations, EGT presents a promising therapeutic strategy for oxidative stress-related ocular diseases such as age-related macular degeneration and diabetic retinopathy. Further studies are warranted to evaluate its long-term efficacy and clinical translation potential.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2022
·
IF 5.895
Luwen Zhang,Jiawei Tang,Meiqing Feng,Shaoxin Chen
Ergothioneine (ERG) is an unusual sulfur-containing amino acid with antioxidant activity that can be synthesized by certain bacteria and fungi. Microbial fermentation is a promising method for ERG production. In this study, the bifunctional enzyme methyltransferase–sulfoxide synthase NcEgt1 from Neurospora crassa was truncated to obtain sulfoxide synthase TNcEgt1, which showed a higher expression level in Escherichia coli BL21(DE3). Then, the genes egtD encoding methyltransferase EgtD and egtE encoding C–S lyase EgtE from Mycobacterium smegmatis were cloned with TncEgt1 into E. coli BL21(DE3) to produce 70 mg/L ERG. To improve ERG production, TNcEgt1 and EgtD were modified, and the resulting mutants were screened with an established high-throughput method which could directly analyze the ERG content in culture broths. After several rounds of mutation and screening, the optimal mutant MD4 was obtained and produced 290 mg/L ERG. Furthermore, a fed-batch culture was conducted in a 5 L bioreactor. After optimizing the fermentation process, the ERG yield reached 5.4 g/L after 94 h of cultivation supplemented with amino acids and glycerol, which is the highest ERG yield reported to date. The results showed that ERG production was significantly improved by modifying the key enzymes, and the engineered strains constructed in this study have potential industrial application prospects.
研究领域:
生物技术
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微生物学
·
酶工程
·
发酵技术
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DOI
PubMed
高影响因子
Microorganisms
·
2026
·Vol. 14
·期 5
·1088
·
IF 4.7
Yuyang Liu,Yaxin Wen,Ruizheng Hu,Ruyue Han,Dong Liu,Hailing Zhang
Ergothioneine (EGT), a naturally occurring amino acid derivative with potent antioxidant and cytoprotective properties, is widely applied in the food, cosmetic, and medical industries. Traditional production methods are limited by high costs, low efficiency, and environmental concerns, so microbial fermentation serves as a sustainable alternative for EGT production. In this study,Escherichia coliBL21 (DE3) was employed as the chassis strain. First, a basic EGT-producing engineered strain was constructed by heterologously expressing theegtBgene fromMethylobacterium pseudosasicolaalong with theegtDandegtEgenes fromMycobacterium smegmatis. This initial strain achieved a yield of 84.84 ± 1.64 mg/L of EGT in shake-flask cultures. To enhance production, solubility-enhancing tags were introduced to improve the soluble expression of the key enzymes, and metabolic pathways were rationally engineered to strengthen the supply of essential precursor amino acids. These modifications led to the development of a high-yield EGT strain. After optimizing the fermentation process, the best results were achieved using a medium with glycerol as the carbon source, 0.5 g/L of histidine, 1.5 g/L of methionine, and 1.0 g/L of cysteine, along with induction at 25 °C using 0.2 mM IPTG for 120 h. Under these conditions, the final EGT yield reached 385.70 ± 4.86 mg/L. The engineered strain for EGT synthesis and optimized fermentation strategy developed in this study offer a useful basis for further process development.
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PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Rongyi Ye,Yihan Wang,Kebo Wang,Nan Huang,Guo Liu,Dexin Gao,Xinru Li,Mengxue Yang,Jing Wang,Chen Chen
Background Non-alcoholic fatty liver disease (NAFLD) represents a burgeoning global health burden with limited pharmacological options. Ergothioneine (EGT), a naturally occurring antioxidant, shows potential hepatoprotective effects; however, the exact mechanisms by which EGT regulates lipid metabolism in NAFLD remain elusive. Purpose This study aimed to investigate the therapeutic efficacy and potential mechanisms of EGT in high-fat diet (HFD)-induced NAFLD. Methods NAFLD was induced in Apo E −/− mice via a 12-week HFD regimen, with concurrent oral administration of low- (1.7 mg/kg) or high-dose (17 mg/kg) EGT. We integrated in vivo multi-omics profiling with in vitro assays to identify the metabolic pathways modulated by EGT. Results EGT administration robustly ameliorated HFD-induced hepatic steatosis, liver injury, and dyslipidemia. We identified a critical regulatory axis wherein EGT inhibits phosphatidylethanolamine cytidylyltransferase 2 (PCYT2) expression, thereby dampening the accumulation of pathogenic phosphatidylethanolamine (PE) species. This suppression of PE synthesis acts as a trigger to upregulate acyl-CoA thioesterase 8 (ACOT8), a key enzyme in lipid turnover. Notably, the protective effects of EGT against palmitic acid-induced lipid accumulation were blunted by the PE synthesis inhibitor meclizine, validating the PE-ACOT8 pathway as the primary target of EGT. Conclusion This study unveils a previously unrecognized mechanism by which EGT alleviates NAFLD: the restoration of the PCYT2/PE/ACOT8 signaling axis. By correcting phospholipid composition to upregulate ACOT8, EGT restores lipid homeostasis, presenting a compelling natural compound-based strategy for NAFLD intervention.
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DOI
高影响因子
ACS Omega
·
2022
·
IF 4.132
Yanju Gao,Bo Zhou,Han Zhang,Lin Chen,Xiaohong Wang,Hongbing Chen,Lin Zhou
Background: Ulcerative colitis (UC) is a chronic disease of the intestinal tract in which excessive activation of inflammatory response is correlated. l-Ergothioneine (EGT) widely existing in mushrooms has various physiological activities. In this study, the protective effects of EGT on dextran sulfate sodium (DSS)-induced colitis mice were investigated. Results: It was observed that EGT administration, especially at the high dose level, prevented the body weight loss, the colon shortening, and the increase in disease activity index and spleen index caused by DSS. Moreover, EGT supplementation attenuated DSS-induced gut barrier damage by enhancing the expression of tight-junction protein and recovering the loss of gut mucus layer. Furthermore, EGT considerably decreased the colonic myeloperoxidase (MPO) activity induced by DSS, but no significant differences were observed in the concentrations of IL-6 and TNF-α in colon tissues. Additionally, EGT downregulated the populations of CD4+ T cells and macrophages, indicating that EGT stabilized the immune response caused by DSS. Conclusion: Together these results suggest that EGT can alleviate DSS-induced colitis and provide important insights concerning the potential anticolitis activity of such food products.
研究领域:
免疫学
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胃肠病学
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药理学
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PubMed
高影响因子
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