Advanced Science
·
2026
·
IF 14.1
Kaiyuan Jiang,Fen Xiong,Yiwen Peng,Lingfei Meng,Xinran Wang,Yingruo Xu,Tian Tang,Hongchang Gao
Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes with limited effective interventions. Using a streptozotocin-induced insulin-deficient, type 1 diabetes-like DCM mouse model, we show that intermittent fasting (IF) improves cardiac function and attenuates myocardial remodeling. Antibiotic-mediated microbiota depletion largely abolished these benefits, whereas fecal microbiota transplantation from IF-treated donors recapitulated cardioprotection, supporting a causal role of the gut microbiota. Metagenomic profiling identified Akkermansia muciniphila ( A. muciniphila ) as a prominent IF-responsive taxon, and A. muciniphila supplementation alleviated cardiac injury without obvious improvement in glycaemia. Integrated serum and heart metabolomics identified 1-methyl-L-histidine as a microbiota-associated metabolite reduced in diabetes but restored by IF and A. muciniphila . In vitro and ex vivo assays further supported an L-anserine-linked microbial route for 1-methyl-L-histidine generation. Importantly, oral 1-methyl-L-histidine supplementation recapitulated key cardioprotective effects, remodeled cardiac lipid homeostasis, and reduced lipid peroxidation and oxidative injury. Together, these findings support a gut microbiota–metabolite–lipid axis associated with IF-related cardioprotection in DCM and highlight microbial metabolites as tractable targets to complement dietary intervention.
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JOURNAL OF FOOD COMPOSITION AND ANALYSIS
·
2026
·
IF 5.3
Mengmeng Feng,Yongkang Luo,Yanfei Jiang,Chunyue Zhao
α-Ketoglutarate (AKG), ergothioneine (EGT), ascorbic acid (VC), and pyrroloquinoline quinone (PQQ) are increasingly co-formulated to combat age-related mitochondrial dysfunction and oxidative stress, driving an urgent need for reliable quality control. However, existing analytical approaches remain fragmented, targeting only one or two compounds, relying on time-consuming derivatization, or employing costly mass spectrometry, and critically failing to address chemical incompatibilities among analytes. This study presents the first validated HPLC-UV method for simultaneous quantification of all four bioactives. A segmented extraction strategy was developed to reconcile their physicochemical conflicts: VC, AKG, and EGT were extracted with 0.1% metaphosphoric acid, while acid-labile PQQ was separately extracted with neutral phosphate buffer. Chromatographic separation was achieved on an AQ-C18 column with a gradient of 50 mM Na₂HPO₄ and acetonitrile. The method demonstrated excellent linearity (R² > 0.99), high sensitivity, good precision (RSD < 2%), and satisfactory accuracy (recoveries: 97.2–103.6%). The Mosaic-WAC score of 82.6 further validates the proposed method. Analysis of commercial products indicated that only VC exhibited degradation, with more pronounced losses in liquid matrices, attributable to its inherent oxidizability. This underscores the need for comprehensive multi-component quality control. The proposed method provides a practical platform for routine analysis and regulatory evaluation of complex nutraceutical products.
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JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 12.4
Renfang-Zhu,Ying Xu,Mingyu Nie,Huiling Li,Ye Yuan,Zhixiang Cui,Hezhi Wang,Qiyao Zhai,Xianhong He,Ying Mao,Yidan Wei,Jian Guan,Xin Zhang,Shirui Mao
Clinically, no effective preventive strategies currently exist to inhibit the progression of early dry age-related macular degeneration (dAMD). Moreover, current retinal therapies rely on intravitreal injections, which carry inherent procedural risks. Inspired by natural melanin and viral structures, we developed virus-biomimetic melanin nanoparticles (VMNPs) surface-modified with ergothioneine (ET), featuring virus-like spike structures and a neutral zwitterionic shell. This study aimed to evaluate whether virus-inspired engineered nanoparticles could enhance retinal delivery and improve the therapeutic potential of melanin-based nanodrugs for dAMD. The VMNPs facilitated cellular uptake through both their virus-mimetic architecture and OCTN1-mediated active transport. They also exhibited potent antioxidant activity, significantly reducing intracellular and mitochondrial reactive oxygen species (ROS) in oxidative stress models of ARPE-19 cells. Transcriptomic analyses revealed that VMNPs activated intrinsic cytoprotective pathways by upregulating HMOX1 and SLC7A11 , while downregulating inflammation-associated genes. Importantly, VMNPs promoted transcytosis and, following topical administration, demonstrated improved retention and deep penetration within the rabbit eye, effectively reaching the retinal pigment epithelium (RPE) and deeper retinal layers. Notably, twice-daily topical administration of VMNPs markedly inhibited retinal degeneration in rabbits, achieving therapeutic efficacy comparable to a single intravitreal injection of pegcetacoplan. Collectively, these findings establish a promising paradigm for the non-invasive clinical treatment of dAMD.
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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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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
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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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2025
·Vol. 122
·期 26
·e2500966122
·
IF 9.1
Yifan Li,Huanhong Lu,Degang Guo,Xiaoyan Li,Fei Qi,Jian Zhang,Reinhard Fischer,Qirong Shen,Zhenzhong Yu
Light controls important biological processes in fungi by regulating transcriptional gene activation. Here, we found that beyond the regulation of mRNA transcript abundance, light regulates alternative splicing (AS) in the filamentous fungi Aspergillus nidulans, Trichoderma guizhouense, and Neurospora crassa. Blue light-regulated AS was involved in ergothioneine biosynthesis and conidiation in T. guizhouense, which required the blue light receptor BLR1. Blue light activated the MAPK HOG (Sak) pathway which then transmitted the signal via the serine/threonine kinase SRK1 to the AS key regulator SRP1. SRK1 and SRP1 are important for light-induced conidiation. The light-activated HOG pathway led to an increase of the SRK1 protein level and its phosphorylation status. Phosphorylated SRK1 translocated from the cytoplasm to the nucleus to interact with SRP1, thereby regulating AS efficiency. This study unravels another level of complexity of fungal environmental sensing and responses and also first describes the entire cascade from an environmental signal to the splicing machinery.
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JOURNAL OF BIOTECHNOLOGY
·
2025
·
IF 3.9
Liang Li,Shanshan Xu,Yanjun Jiang
Ergothioneine (ERG) is a potent antioxidant with applications in nutrition, pharmaceuticals, dermatology, and related fields. However, its large-scale production is constrained by low yields and high costs linked to extraction and chemical synthesis. Microbial fermentation offers a promising alternative. In this study, a truncated NcEgt1–1 from Neurospora crassa and CtEgtB from Chloracidobacterium thermophilum were fused to convert L-histidine and L-cysteine into hercynylcysteine sulfoxide, subsequently catalyzed by MsEgtE from Mycobacterium smegmatis to produce ERG. Initial expression in Escherichia coli yielded 87.02 mg/L of ERG. With the use of a rigid linker-EAAAK, the ERG titer increased to 144 mg/L. Further amino acid modifications in NcEgt1–1 resulted in the mutant strain M3–02, producing 325 mg/L of ERG. Fed-batch fermentation in a 5-L bioreactor achieved an ERG yield of 790 mg/L with a productivity of 9 mg/L/h. Iterative mutations of CtEgtB further increased ERG production to 478 mg/L in shake flasks and 790 mg/L in the bioreactor, with productivity rising to 14.9 mg/L/h. This study presents an engineered strain with significant ERG production potential, suitable for industrial application.
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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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Food Chemistry-X
·
2025
·
IF 8.2
Yong Li,Jingyu Liu,Junlong Meng,Cuiping Feng,Jie Chen,Maomao Zeng,Hua Li
This study investigated the formation of harmful Maillard reaction products (MRPs), particularly advanced glycation end products (AGEs) and 1,2-dicarbonyl compounds, in fried shiitake mushroom crisps prepared from ten types of Lentinula edodes , in relation to their inherent chemical components. Analyzed harmful MRPs included 1,2-dicarbonyls (3-deoxyglucosone/3-DG, glyoxal/GO, methylglyoxal/MGO, diacetyl/DA), hydroxymethylfurfural/HMF, and AGEs (carboxymethyllysine/CML, carboxyethyllysine/CEL, methylglyoxal-derived hydroimidazolone1/MG-H1). Results revealed the positive effect of glucose, 3-DG, Asp, Arg, and Lys on the HMF levels. Conversely, ergothioneine negatively correlated with 3-DG, DA, MGO, CML, and CEL; vanillic acid and caffeic acid were inversely related to GO and MG-H1, respectively. Additionally, Ser positively correlated with CML, while CEL had significant negative correlations with Asp, Gly, and total free amino acid. Overall, there was a complex relationship between the chemical components and harmful MRPs in fried shiitake crisps, with ergothioneine, caffeic acid, and vanillic acid showing potential inhibitors of AGEs and 1,2-dicarbonyls generation.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
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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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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