FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Wen Gao,Yang Wang,Fuhao Wang,Xinni Wu,Fuping Lu,Fufeng Liu
Ergothioneine (EGT) is a natural dietary antioxidant derived from certain edible mushrooms, commonly used as a food additive and supplement, but its effects on Parkinson’s Disease (PD) are still unclear. The accumulation of α-synuclein (α-syn) plays a pivotal role in the pathogenesis and development of PD. Here, this study demonstrated that EGT effectively inhibits α-syn aggregation, disrupts mature fibers, and reduces associated cytotoxicity and oxidative stress. The beneficial effects of EGT were confirmed in Caenorhabditis elegans , where it protected dopaminergic neurons, prolonged lifespan and enhanced behavioral functions by reducing α-syn plaque accumulation and associated oxidative stress. Molecular dynamics simulation revealed that EGT interacts directly with α-syn pentamer through van der Waals and electrostatic forces, disrupting the structural stability of the preformed pentamer. Furthermore, animal studies validated that EGT alleviated neuronal damage and improved behavioral deficits by reducing α-syn aggregation, oxidative stress and inflammatory response. In conclusion, EGT presents promising potential as a dietary supplement for preventing and alleviating PD.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2025
·
IF 2.2
Qiuni Long,Hua Huang,Xinshuai Zhang
l -ergothioneine is a naturally occurring histidine thio-derivative produced by certain bacterial and fungal species. Plants acquire ergothioneine from soil, while animals ingest it through their diets. Ergothioneine is widely acknowledged for its powerful antioxidant properties, capable of scavenging reactive oxygen and nitrogen species, thereby exhibiting promising applications across various industrial fields such as cosmetics, functional foods, and medicine. The catabolism of ergothioneine in the biosphere is quite diversified, in this study, we successfully analyzed and experimentally characterized an oxidative catabolic pathway of ergothioneine encoded by Actinoplanes missouriensis ATCC 14538. In this pathway, ergothioneine is firstly oxidized into ergothioneine sulfinate under the catalysis of a dioxygenase (PF05995). Then, ergothioneine sulfinate is converted into hercynine by releasing sulfite with an aminohydrolase (SSF51556). Finally, hercynine is transformed into urocanate, a known metabolite in histidine catabolism, by an aromatic amino acid lyase (PF00221). This catabolic pathway is primarily present in Actinobacteria, a group of soil microorganisms that may capable of recycling sulfur of ergothioneine through this pathway.
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Antioxidants
·
2026
·Vol. 15
·期 9
·1064
·
IF 8.2
Yuri P. Tsentalovich,Nataliya A. Osik,Maxim V. Fomenko,Nikita A. Dmitriev,Vadim V. Yanshole
Ergothioneine (ESH) is one of the most abundant antioxidants in the human body, but its biological functions remain unclear. In this work, we elucidated the detailed mechanism of the deactivation of divalent copper ions Cu(II) by ESH using optical spectroscopy, NMR, and LC-MS. We found that the reduction of Cu(II) ions to Cu(I) by ESH occurs in a bimolecular reaction of CuII(ES−)2complexes, leading to the formation of the disulfide ESSE. Cu(I) ions remain bound in stable complexes with ESH, preventing their reactions with molecular oxygen. Over longer timescales, ESSE decomposes, regenerating reduced ESH and forming the final reaction product, hercynine (EH). The conversion of one ESH molecule to EH causes the reduction of four Cu(II) ions. We determined the rate constants of the bimolecular reaction between CuII(ES−)2complexes to be k3= (8 ± 4) × 104M−1s−1and of ESSE hydrolysis to be k4= (1.7 ± 0.4) × 10−5s−1and also estimated the formation constant K12≈ 1.2 × 1017M−2for the CuII(ES−)2complex. The high efficiency of Cu(II) reduction and the chelation of the resulting Cu(I) ions in a stable complex supports the hypothesis that protecting cells from oxidation by metal ions is likely one of the main functions of ESH.
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PLoS One
·
2026
·Vol. 21
·期 6
·e0351630
·
IF 2.8
Jiaxin Peng,Jing Chen,Zhipu Qian,Mingzhang Han,Ling Chen
This study investigates the role and mechanism of ergothioneine (EGT) in mitigating the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). Using a cisplatin-induced mouse model of the AKI-to-CKD transition with EGT intervention, we combined histopathological examination, biochemical assays, and single-cell RNA sequencing (scRNA-seq) to provide evidence that EGT may improve renal function parameters and attenuate renal injury and fibrosis. scRNA-seq analysis revealed that EGT was associated with partial normalization of mitochondria-related gene expression in renal tubular epithelial cells, accompanied by enrichment of oxidative phosphorylation and electron transport chain pathways. Furthermore, our in vitro experiments supported a protective association of EGT with mitochondrial injury-related phenotypes in injured renal tubular epithelial cells, as indicated by reduced reactive oxygen species generation, partial preservation of mitochondrial membrane potential, and increased cellular ATP levels. These findings suggest that EGT may attenuate AKI-to-CKD progression in association with improved mitochondrial homeostasis, offering a potential therapeutic strategy for kidney diseases.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yamiao Li,Jingxin Rao,Zhentao Jiang,Xinyi Zhang,Qiang Zhu,Caokai Zhu,Wenli Yu,Xin Dong,Shanshan Gao,Wenchi Zhang,Liang Lin,Mingyue Zheng,Rongzhen Zhang
Ergothioneine (ERG), a sulfur-containing natural antioxidant with significant biomedical potentials, has long been limited by low productivity in microbial fermentation. Here, we report the first high-efficiency in vitro reconstruction of a multi-enzyme cascade for ERG biosynthesis. To address the rate-limiting histidine methylation step, we employed a synergistic strategy integrating machine learning–based kinetic prediction (CataPro, DLkcat), molecular dynamics simulations, and conformational dynamics analysis to guide site-directed mutagenesis of Mycolicibacrterium smegmatis EgtD. This yielded a triple mutant M3 (L53A/T59S/E282S) with 3.4- and 2.8-fold enhancements in catalytic efficiency ( k cat / K m ) toward histidine and S-adenosyl-L-methionine (SAM), respectively. Mechanistically, M3 enhances catalysis by reducing the SAM-histine distance, optimizing the catalytic angle, eliminating non-productive hydrogen bonds, and unlocking a secondary ligand tunnel through a mutation-induced gating mechanism. When coupled with a SAM-regeneration module, the engineered cascade enables preparative-scale ERG synthesis, reaching a titer of 6.05 g·L −1 within 14.5 h and productivity of 10.01 g·L −1 d −1 —the highest report to date. This work showcases a structure-guided, AI-assisted approach that overcomes evolutionary constraints, unlocks latent reactivity, and accelerates the development of efficient biocatalytic cascades for high-value compound synthesis.
研究领域:
合成生物学
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酶工程
·
计算生物学
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生物催化
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代谢工程
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结构生物学
·
机器学习在生物技术中的应用
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Jiahuan Ling,Rui Chen,Minghai Wang,Chun-Xiao Yan,Ruomu Xia,Lihui Zhang
Ergothioneine (EGT) is a powerful and natural antioxidant, which can protect cells in the human body from oxidative damage. Numerous studies have attempted to enhance the heterologous synthesis. However, research on EGT transport out of Escherichia coli cells and the wild-type enzyme from Trichoderma reesei is rare. Here, membrane permeability engineering and protein engineering are combined to improve EGT production in E. coli. After metabolic engineering to enhance precursor supply, we deleted the genes involved in lipopolysaccharide biosynthesis to increase the membrane permeability, which promoted EGT production. Further, a mutant of Tregt2E155C with improved catalytic capacity was created, and the expression level of enzymes involved in EGT synthesis was optimized. Finally, fermentation parameters were systematically tuned to maximize the EGT production. The engineered strain MT9-PET-T1/RSF-T2E155C produced 334.20 ± 6.33 mg/L EGT during 48 h of shake-flask fermentation, corresponding to an 8.4-fold increase compared with wild-type strain MT1. When scaled up to 5 L bioreactors, the strain achieved a final EGT titer of 4.06 g/L within 96 h (42.29 mg/L/h). Our work shows significant implications for EGT synthesis and is also a reference for manipulating E. coli to synthesize other biomolecules.
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Metabolites
·
2025
·Vol. 15
·期 1
·45
·
IF 3.7
Zhe Liu,Fengxu Xiao,Yupeng Zhang,Jiawei Lu,Youran Li,Guiyang Shi
Purpose: This study aimed to utilize genetically engineeredBacillus licheniformisfor the production of ergothioneine (EGT). Given the value of EGT and the application ofBacillus licheniformisin enzyme preparation production, we cloned the key enzymes (EanA and EanB) fromChlorbium limicola. Through gene alignment, new ergothioneine synthase genes (EanAN and EanBN) were identified and then expressed inBacillus licheniformisto construct strains. Additionally, we investigated the factors influencing the yield of EGT and made a comparison withEscherichia coli. Methods: The relevant genes were cloned and transferred intoBacillus licheniformis. Fermentation experiments were conducted under different conditions for yield analysis, and the stability of this bacterium was also evaluated simultaneously. Results: The constructed strains were capable of producing EGT. Specifically, the yield of the EanANBN strain reached (643.8 ± 135) mg/L, and its stability was suitable for continuous production. Conclusions: Genetically engineeredBacillus licheniformisdemonstrates potential in the industrial-scale production of EGT. Compared withEscherichia coli, it has advantages, thus opening up new possibilities for the application and market supply of EGT.
研究领域:
微生物学
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生物技术
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分子生物学
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TRENDS IN BIOTECHNOLOGY
·
2025
·
IF 14.9
Junjun Yan,Yunhong Chen,Yuyue Ma,Xue Yang,Yonghong Yao,Guoping Zhao,Yanfei Zhang
Ergothioneine (ERG) is a rare amino acid with diverse biological activities, making it valuable for applications in the food, cosmetics, and pharmaceutical industries. Compared with traditional extraction from edible fungi, microbial fermentation offers a more scalable alternative, but its feasibility is largely determined by production titer and cost. In this study, we developed a novel ERG biosynthesis strategy that eliminates the need for expensive methionine and cysteine supplementation during fermentation. By reconstructing a betaine-driven methyl supply system and an inorganic sulfur supply module in Escherichia coli , we engineered a highly efficient ERG-producing strain capable of utilizing betaine as a methyl donor and inorganic sulfur as a sulfur source. As a result, shake flask fermentations achieved an ERG titer of 456 ± 9 mg/l without exogenous methionine and cysteine supplementation. Further optimization strategies, including enhanced intracellular histidine synthesis, alleviation of methionine feedback inhibition, and improved ERG transport efficiency, increased the shake flask titer to 1.2 g/l, a 24-fold improvement over the initial strain. Scale-up in a 5-l fermenter further optimized fermentation conditions, yielding an ERG titer of 7.2 g/l. Thus, the metabolic engineering strategy described in this study provides a scalable and cost-effective platform for the industrial production of ERG and other methyl- and sulfur-containing natural products.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
·
IF 6.7
Wang Suyu,Zabed Hossain M.,Zhang Guoyan,Yun Junhua,Tian Yuehui,Zhang Yufei,Qi Xianghui
Ergothioneine (EGT) is a high-value antioxidant for food,
pharmaceutical,
nutraceutical, and cosmetic applications. Microbial production from
renewable feedstocks is promising, but efficient biosynthesis requires
coordinated precursor supply. Precursor-supplementation experiments
indicated that multiple amino acids may jointly influence EGT production.
Based on pathway biochemistry and previous engineering evidence, endogenous l -cysteine supply was selected as one mechanistically relevant
engineering target. Here, an Escherichia coli platform for glucose-derived EGT production was developed by combining
biosensor-driven evolution and transcriptome-guided chassis engineering.
A dual-output l -cysteine-responsive biosensor linked kanamycin
resistance and fluorescence, enabling sequential growth-based enrichment
and fluorescence-based prioritization. Mutagenesis, microdroplet-assisted
adaptive evolution, and single-cell sorting generated an evolved chassis
with 47.10% higher extracellular l -cysteine accumulation
and 64.49% higher EGT production. Transcriptome-guided bsmA activation further improved production, and the final strain produced
1.20 g/L EGT in a 3 L fed-batch fermentation without additional l -cysteine supplementation.
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Food Bioscience
·
2025
·
IF 5.9
Lei Chen,Zhuomin Zhang,Zihan Guan,Jing Sun,Yanhui Sun,Mengmeng Xu,Ka-Hing Wong,Guiyang Shi,Zhongyang Ding
Ergothioneine (EGT) production in Pleurotus tuber-regium was significantly enhanced through Na 2 SeO 3 -induced oxidative stress, in combination with optimized carbon sources and precursor amino acids. Initially, glucose and rhamnose (20 g/L each) as dual carbon sources increased EGT synthesis. Supplementation with 0.75 mM cysteine and 1 mM methionine further promoted EGT biosynthesis by providing essential precursors. Additionally, the introduction of 0.3 mM Na 2 SeO 3 induced oxidative stress, leading to an EGT accumulation of 4.68 mg/g dry weight (DW) in the mycelium and a yield of 35.27 mg/L, representing a 4.25-fold and 162% increases compared to the control, respectively. RNA-Seq analysis revealed that selenium exposure triggered the upregulation of genes involved in antioxidant defense, reinforcing redox homeostasis and driving EGT accumulation. This study highlights the mechanistic role of selenium in modulating antioxidant pathways, offering a promising strategy for enhancing EGT production in the nutraceutical and biotechnological fields.
研究领域:
生物技术
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营养学
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分子生物学
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ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Yaping Liu,Chengyan Wang,Ruixue Liu,Maoru Zhao,Xuefeng Ding,Tingjun Zhang,Rendong He,Shuang Zhu,Xinghua Dong,Jiani Xie,Zhanjun Gu,Yuliang Zhao
Radiation gastroenteritis represents one of the most prevalent and hazardous complications of abdominopelvic radiotherapy, which not only severely reduces patients’ life quality but also restricts radiotherapy efficacy. However, there is currently no clinically available oral radioprotector for this threatening disease due to its complex pathogenesis and the harsh gastrointestinal environment. To this end, this study developed a facile but effective oral radioprotector, ergothioneine hyaluronate (EGT@HA) gel, protecting against radiation gastroenteritis by synergistically regulating oxidative stress, inflammation, and gut microbiota. In vitro and cellular experiments verified the chemical stability and free radical scavenging ability of EGT and its favorable cellular radioprotective efficacy by inhibiting intracellular reactive oxidative species (ROS) generation, DNA damage, mitochondrial damage, and apoptosis. At the in vivo level, EGT@HA with prolonged gastrointestinal residence mitigated radiation-induced gastrointestinal tissue injury, apoptosis, neutrophil infiltration, and gut flora dysbiosis. For the first time, this work investigated the protective effects of EGT@HA gel on radiation gastroenteritis, which not only hastens the advancement of the novel gastrointestinal radioprotector but also provides a valuable gastrointestinal radioprotection paradigm by synergistically modulating oxidative stress, inflammation, and gut microbiota disturbance.
研究领域:
药理学
·
放射生物学
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胃肠病学
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生物医学工程
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微生物学
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JOURNAL OF BIOTECHNOLOGY
·
2025
·
IF 3.9
Yu-Zhen Li,Qi Wang,Cheng Cheng,Chao Chen,Feng-Li Zhang,Yue Zou,Jun Li,Xin-Qing Zhao
Endophytic yeast strains are promising sources of various valuable bioactive compounds. However, studies on endophytic strains derived from lichen samples remains limited. In this study, we isolated and characterized Rhodotorula sp. Y090 from Usnea longissima and investigated its biosynthetic potential. Genome mining revealed distinct genetic features that differed from its closest relative strain R. graminis WP1. Ergothioneine (EGT) is a potent antioxidant and rare sulfur-containing histidine derivative. However, so far, the EGT biosynthetic enzymes by natural yeast strains have been limitedly studied. In this study, combining genome mining and transcriptomic analysis, genes encoding the potential enzymes for the production of EGT and xylose utilization were identified in Rhodotorula sp. Y090. Further studies demonstrated that Rhodotorula sp. Y090 was capable of producing EGT using xylose, glucose, glycerol, and sucrose as the sole carbon sources, and the highest titer reached 363.6 mg/L in shake flask culture, which is significantly higher than that of the most reported levels in the other natural yeasts. Rhodotorula sp. Y090 also exhibited a good ability of EGT export, which could facilitate cost-effective production. These findings suggest that the lichen-derived endophytic yeast Rhodotorula sp. Y090 represents a promising natural candidate for bio-production of the potent antioxidant.
研究领域:
微生物学
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生物化学
·
基因组学
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