Recombinant Aflatoxin-Degrading F<sub>420</sub>H<sub>2</sub>-Dependent Reductase from <i>Mycobacterium smegmatis</i> Protects Mammalian Cells from Aflatoxin Toxicity
Aflatoxins are carcinogenic secondary metabolites of fungi that contaminate many staple crops and foods. Aflatoxin contamination is a worldwide problem, especially in developing countries, posing health hazards, e.g., causing aflatoxicosis and hepatocellular carcinoma, and even death. Biological sol...
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| Format: | Article |
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MDPI AG
2019-05-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/11/5/259 |
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| author | Che-Hsing Li Wei-Yang Li I-Ning Hsu Yung-Yu Liao Chi-Ya Yang Matthew C. Taylor Yu-Fan Liu Wei-Hao Huang Hsiang-Hua Chang Ho-Lo Huang Shao-Chi Lo Ting-Yu Lin Wei-Che Sun Ya-Yi Chuang Yu-Chieh Yang Ru-Huei Fu Rong-Tzong Tsai |
| author_facet | Che-Hsing Li Wei-Yang Li I-Ning Hsu Yung-Yu Liao Chi-Ya Yang Matthew C. Taylor Yu-Fan Liu Wei-Hao Huang Hsiang-Hua Chang Ho-Lo Huang Shao-Chi Lo Ting-Yu Lin Wei-Che Sun Ya-Yi Chuang Yu-Chieh Yang Ru-Huei Fu Rong-Tzong Tsai |
| author_sort | Che-Hsing Li |
| collection | DOAJ |
| description | Aflatoxins are carcinogenic secondary metabolites of fungi that contaminate many staple crops and foods. Aflatoxin contamination is a worldwide problem, especially in developing countries, posing health hazards, e.g., causing aflatoxicosis and hepatocellular carcinoma, and even death. Biological solutions for aflatoxin detoxification are environmentally friendly and a cheaper alternative than chemical methods. The aims of the current study were to investigate: (1) the ability of MSMEG_5998, an aflatoxin-degrading F<sub>420</sub>H<sub>2</sub>-dependent reductase from <i>Mycobacterium smegmatis</i>, to degrade aflatoxin B1 (AFB1) and reduce AFB1-caused damage in HepG2 cell culture model; and (2) whether a thioredoxin (Trx) linkage of MSMEG_5998 enhanced the enzyme activity. We show that Trx-linked MSMEG_5998 degraded 63% AFB1 and native MSMEG_5998 degraded 31% after 4 h at 22 °C, indicating that the Trx-linked enzyme had a better AFB1-degrading ability. In a HepG2 cell culture model, Trx-linked MSMEG_5998 reduced DNA damage and p53-mediated apoptosis caused by AFB1 to a greater extent than the native enzyme. These findings suggest that Trx-linked MSMEG_5998 could potentially be developed to protect the liver from AFB1 damage, or as a candidate protein to reduce AFB1-related toxicity in animals. |
| first_indexed | 2024-04-11T17:59:59Z |
| format | Article |
| id | doaj.art-ace3ea632a564bed9392cfe86689ae66 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T17:59:59Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-ace3ea632a564bed9392cfe86689ae662022-12-22T04:10:33ZengMDPI AGToxins2072-66512019-05-0111525910.3390/toxins11050259toxins11050259Recombinant Aflatoxin-Degrading F<sub>420</sub>H<sub>2</sub>-Dependent Reductase from <i>Mycobacterium smegmatis</i> Protects Mammalian Cells from Aflatoxin ToxicityChe-Hsing Li0Wei-Yang Li1I-Ning Hsu2Yung-Yu Liao3Chi-Ya Yang4Matthew C. Taylor5Yu-Fan Liu6Wei-Hao Huang7Hsiang-Hua Chang8Ho-Lo Huang9Shao-Chi Lo10Ting-Yu Lin11Wei-Che Sun12Ya-Yi Chuang13Yu-Chieh Yang14Ru-Huei Fu15Rong-Tzong Tsai16School of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Horticulture and Landscape Architecture, National Taiwan University, Taipei 10617, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanLand and Water, CSIRO, GPO Box 1700, Canberra, ACT 2601, AustraliaDepartment of Biomedical Science, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Life Science, National Taiwan University, Taipei 10617, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Electrical Engineering, National Chung Hsing University, Taichung 402, TaiwanDepartment of Electrical Engineering, National Chung Hsing University, Taichung 402, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanTranslational Medicine Research Center, China Medical University Hospital, Taichung 40447, TaiwanInstitute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, TaiwanAflatoxins are carcinogenic secondary metabolites of fungi that contaminate many staple crops and foods. Aflatoxin contamination is a worldwide problem, especially in developing countries, posing health hazards, e.g., causing aflatoxicosis and hepatocellular carcinoma, and even death. Biological solutions for aflatoxin detoxification are environmentally friendly and a cheaper alternative than chemical methods. The aims of the current study were to investigate: (1) the ability of MSMEG_5998, an aflatoxin-degrading F<sub>420</sub>H<sub>2</sub>-dependent reductase from <i>Mycobacterium smegmatis</i>, to degrade aflatoxin B1 (AFB1) and reduce AFB1-caused damage in HepG2 cell culture model; and (2) whether a thioredoxin (Trx) linkage of MSMEG_5998 enhanced the enzyme activity. We show that Trx-linked MSMEG_5998 degraded 63% AFB1 and native MSMEG_5998 degraded 31% after 4 h at 22 °C, indicating that the Trx-linked enzyme had a better AFB1-degrading ability. In a HepG2 cell culture model, Trx-linked MSMEG_5998 reduced DNA damage and p53-mediated apoptosis caused by AFB1 to a greater extent than the native enzyme. These findings suggest that Trx-linked MSMEG_5998 could potentially be developed to protect the liver from AFB1 damage, or as a candidate protein to reduce AFB1-related toxicity in animals.https://www.mdpi.com/2072-6651/11/5/259aflatoxin B1F<sub>420</sub>H<sub>2</sub>-dependent reductaseMSMEG_5998thioredoxindeazaflavin |
| spellingShingle | Che-Hsing Li Wei-Yang Li I-Ning Hsu Yung-Yu Liao Chi-Ya Yang Matthew C. Taylor Yu-Fan Liu Wei-Hao Huang Hsiang-Hua Chang Ho-Lo Huang Shao-Chi Lo Ting-Yu Lin Wei-Che Sun Ya-Yi Chuang Yu-Chieh Yang Ru-Huei Fu Rong-Tzong Tsai Recombinant Aflatoxin-Degrading F<sub>420</sub>H<sub>2</sub>-Dependent Reductase from <i>Mycobacterium smegmatis</i> Protects Mammalian Cells from Aflatoxin Toxicity Toxins aflatoxin B1 F<sub>420</sub>H<sub>2</sub>-dependent reductase MSMEG_5998 thioredoxin deazaflavin |
| title | Recombinant Aflatoxin-Degrading F<sub>420</sub>H<sub>2</sub>-Dependent Reductase from <i>Mycobacterium smegmatis</i> Protects Mammalian Cells from Aflatoxin Toxicity |
| title_full | Recombinant Aflatoxin-Degrading F<sub>420</sub>H<sub>2</sub>-Dependent Reductase from <i>Mycobacterium smegmatis</i> Protects Mammalian Cells from Aflatoxin Toxicity |
| title_fullStr | Recombinant Aflatoxin-Degrading F<sub>420</sub>H<sub>2</sub>-Dependent Reductase from <i>Mycobacterium smegmatis</i> Protects Mammalian Cells from Aflatoxin Toxicity |
| title_full_unstemmed | Recombinant Aflatoxin-Degrading F<sub>420</sub>H<sub>2</sub>-Dependent Reductase from <i>Mycobacterium smegmatis</i> Protects Mammalian Cells from Aflatoxin Toxicity |
| title_short | Recombinant Aflatoxin-Degrading F<sub>420</sub>H<sub>2</sub>-Dependent Reductase from <i>Mycobacterium smegmatis</i> Protects Mammalian Cells from Aflatoxin Toxicity |
| title_sort | recombinant aflatoxin degrading f sub 420 sub h sub 2 sub dependent reductase from i mycobacterium smegmatis i protects mammalian cells from aflatoxin toxicity |
| topic | aflatoxin B1 F<sub>420</sub>H<sub>2</sub>-dependent reductase MSMEG_5998 thioredoxin deazaflavin |
| url | https://www.mdpi.com/2072-6651/11/5/259 |
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