CHEMISTRY & BIODIVERSITY
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2025
·
IF 2.5
Tao Xuan Vu,Minh-Trung Nguyen,Anh Ngoc Dao,Tram Bao Tran,Yen Thi Hoang Le,Van-Tuan Tran,Thu-Huong Nguyen,Quang-Vinh Nguyen
Cordyceps militaris is a medicinal fungus known for its immunomodulatory effects. This study compared the antioxidant and anti-inflammatory activities of an albino strain ( C. militaris SHBTQ) and its wild-type counterpart (SHQ) using ethanol extracts from their fruiting bodies. The albino strain exhibited significantly higher bioactive compound levels, with cordycepin and pentostatin concentrations 2.37- and 1.74-fold higher than in the wild type. Enhanced polyphenol and flavonoid content correlated with stronger 1,1-diphenyl-2-picrylhydrazyl and azino-bis-(3-ethylbenzothiazoline sulfonate) radical scavenging (2.67- and 1.91-fold higher) and superior copper-chelating ability (97.52% vs. 51.83% at 5 mg/L). It also demonstrated greater anti-inflammatory effects, with a lower 50% inhibitory concentration in the bovine serum albumin denaturation assay (7.42 vs. 14.49 mg/mL) and reduced oxidative stress in zebrafish models. The superior bioactivity of SHBTQ, likely due to its high bioactive compound content, underscores its therapeutic potential against oxidative stress-related diseases. Graphical
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Fermentation-Basel
·
2023
·Vol. 9
·期 4
·398
·
IF 3.7
Hongyu Zhang,Deguang Zhang,Ran Liu,Tingting Lou,Ruyue Tan,Suying Wang
The special structure of pentostatin causes it to possess a wide spectrum of biological and pharmacological properties, and it has been extensively employed to treat malignant tumors and is the first-line treatment for hairy cell leukemia. Pentostatin is mainly distributed in several actinomycetes and fungi species. However, its low titer in microbes is not able to meet medical needs. Here, we report a strain improvement strategy based on combined atmospheric and room-temperature plasma (ARTP) mutagenesis and ribosome engineering screening, as well as fermentation optimization, for enhanced pentostatin production. The original strain,Actinomadurasp. ATCC 39365, was treated with ARTP and screened by ribosome engineering to obtain one stable pentostatin high-yield mutantActinomadurasp. S-15, which produced 86.35 mg/L pentostatin, representing a 33.79% increase compared toActinomadurasp. ATCC 39365. qRT-PCR analysis revealed that pentostatin biosynthesis-related gene expression was significantly upregulated inActinomadurasp. S-15. Then, to further enhance pentostatin production, the fermentation medium was optimized in flask culture and the pentostatin production ofActinomadurasp. S-15 reached 152.06 mg/L, which is the highest pentostatin production reported so far. These results demonstrate the effectiveness of combined ARTP mutation, ribosome engineering screening, and medium optimization for the enhancement of pentostatin production, and provide a methodology enabling the sustainable production of pentostatin on an industrial scale.Keywords:Actinomadurasp.;pentostatin;atmospheric and room temperature plasma;ribosome engineering
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FOLIA MICROBIOLOGICA
·
2019
·Vol. 65
·期 2
·293-302
·
IF 1.448
Zhang Xin-guo,Sun Qiao-Yun,Tang Peng,Ma Guo-Yan,Guo Guang-Jun,Guo Si-Jia,Ma Xiao-Di
Medicinal plants have been studied for potential endophytic interactions and numerous studies have provided evidence that seeds harbor diverse microbial communities, not only on their surfaces but also within the embryo. Adenosine deaminase (ADA) is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Therefore, in this study, 20 types of medicinal plant seeds were used to screen endophytic fungi with tissue homogenate and streak. In addition, 128 morphologically distinct endophyte strains were isolated and their ADA inhibitory activity determined by a spectrophotometric assay. The strain with the highest inhibitory activity was identified as Cochliobolus sp. Seven compounds were isolated from the strain using a chromatography method. Compound 3 showed the highest ADA inhibitory activity and was identified as 5-hydroxy-2-hydroxymethyl-4H-pyran-4-one, based on the results of 1H and 13C NMR spectroscopy. The results of molecular docking suggested that compound 3 binds to the active site and the nonspecific binding site of the ADA. Furthermore, we found that compound 3 is a mixed ADA inhibitor. These results indicate that endophytic strains are a promising source of ADA inhibitors and that compound 3 may be a superior source for use in the preparation of biologically active ADA inhibitor compounds used to treat cancer.
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ACS Nano
·
2025
·
IF 16
Si-Min Zeng,Wen-Qiang Qu,Yu-Liang Sun,Ke-Wei Chen,Kai Zhao,Jian-Hua Yan,Cheng Zhang,Chun-Xiao Liang,Yu Chen,Ting Pan,Aixi Yu,Xian-Zheng Zhang
Hypoxia-related adenosine (Ado) exerts an immunosuppressive effect in tumors by binding to the metabolic checkpoint Ado A2A receptors (A2AR), thereby hindering the activation of antitumor immunity induced by immunogenic cell death (ICD). In this study, a MnO2-assisted photosynthetic bacteria (PSB) biohybrid (MnO2@PSB) is developed to enhance tumor photothermal immunotherapy by interfering with the Ado-A2AR metabolic pathway. Specifically, manganese dioxide (MnO2) nanoflowers are conjugated onto PSB by the carbodiimide reaction to construct the biohybrid MnO2@PSB. As a photothermal agent, MnO2@PSB generates heat to “burn” tumor cells under 808 nm laser irradiation, inducing tumor cell ICD. Meanwhile, MnO2@PSB catalyzes the decomposition of endogenous hydrogen peroxide into oxygen to alleviate tumor hypoxia, thereby reducing Ado production and downregulating the expression of A2AR, further reversing the tumor immunosuppressive microenvironment and amplifying the ICD effects. In various mouse 4T1 tumor models, MnO2@PSB can enhance antitumor immune responses, prolong mouse survival, and significantly inhibit tumor growth, recurrence, and metastasis under 808 nm laser irradiation. Collectively, this study provides a direction for enhanced antitumor immunotherapy through regulating metabolic pathways.
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CURRENT MICROBIOLOGY
·
2017
·Vol. 75
·期 5
·565-573
·
IF 1.322
Zhang Xin-guo,Liu Jin-wen,Tang Peng,Liu Zi-yu,Guo Guang-Jun,Sun Qiao-Yun,Yin Jian-jun
Adenosine deaminase (ADA) is an enzyme widely distributed from bacteria to humans. ADA is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Endophytes are endosymbionts, often bacteria or fungi, which live within plant tissues and internal organs or intercellular space. Endophytes have a broad variety of bioactive metabolites that are used for the identification of novel natural compounds. Here, 54 morphologically distinct endophyte strains were isolated from six plants such as Peganum harmala Linn., Rheum officinale Baill., Gentiana macrophylla Pall., Radix stephaniae tetrandrae, Myrrha , and Equisetum hyemale Linn. The isolated strains were used for the search of ADA inhibitors that resulted in the identification of the strain with the highest inhibition activity, Aspergillus niger sp. Four compounds were isolated from this strain using three-step chromatography procedure, and compound 2 was determined as the compound with the highest inhibition activity of ADA. Based on the results of 1 H and 13 C NMR spectroscopies, compound 2 was identified as 3-(4-nitrophenyl)-5-phenyl isoxazole. We showed that compound 2 was a new uncompetitive inhibitor of ADA with high cytotoxic effect on HepG2 and SMCC-7721 cells (the IC 50 values were 0.347 and 0.380 mM, respectively). These results suggest that endophyte strains serve as promising sources for the identification of ADA inhibitors, and compound 2 could be an effective drug in the cancer treatment.
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