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Recombinant Aflatoxin-Degrading F420H2-Dependent Reductase from Mycobacterium smegmatis Protects Mammalian Cells from Aflatoxin Toxicity

1
School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
2
Department of Horticulture and Landscape Architecture, National Taiwan University, Taipei 10617, Taiwan
3
Land and Water, CSIRO, GPO Box 1700, Canberra, ACT 2601, Australia
4
Department of Biomedical Science, Chung Shan Medical University, Taichung 40201, Taiwan
5
Department of Life Science, National Taiwan University, Taipei 10617, Taiwan
6
Department of Electrical Engineering, National Chung Hsing University, Taichung 402, Taiwan
7
Translational Medicine Research Center, China Medical University Hospital, Taichung 40447, Taiwan
8
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan
9
Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed to the work equally and should be regarded as co-third authors.
Toxins 2019, 11(5), 259; https://doi.org/10.3390/toxins11050259
Received: 30 March 2019 / Revised: 30 April 2019 / Accepted: 6 May 2019 / Published: 8 May 2019
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Abstract

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 F420H2-dependent reductase from Mycobacterium smegmatis, 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. View Full-Text
Keywords: aflatoxin B1; F420H2-dependent reductase; MSMEG_5998; thioredoxin; deazaflavin aflatoxin B1; F420H2-dependent reductase; MSMEG_5998; thioredoxin; deazaflavin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Li, C.-H.; Li, W.-Y.; Hsu, I.-N.; Liao, Y.-Y.; Yang, C.-Y.; Taylor, M.C.; Liu, Y.-F.; Huang, W.-H.; Chang, H.-H.; Huang, H.-L.; Lo, S.-C.; Lin, T.-Y.; Sun, W.-C.; Chuang, Y.-Y.; Yang, Y.-C.; Fu, R.-H.; Tsai, R.-T. Recombinant Aflatoxin-Degrading F420H2-Dependent Reductase from Mycobacterium smegmatis Protects Mammalian Cells from Aflatoxin Toxicity. Toxins 2019, 11, 259.

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