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Antioxidants Used by Deinococcus Radiodurans and Implications for Antioxidant Drug Discovery

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CORRESPONDENCE LINK TO ORIGINAL ARTICLE LINK TO AUTHOR’s REPLY In summary, it seems that the antioxi- dant defence system of D. radiodurans Antioxidants used by Deinococcus consists of several lines of antioxidants, including enzymes and non-enzymatic radiodurans and implications for small molecules, which is directly relevant to antioxidant drug discovery. Lipoic antioxidant drug discovery acid has been approved as an antioxidant drug, and therefore the other antioxidants used by D. radiodurans (that is, Mn(II) Hong-Yu Zhang, Xue-Juan Li, Na Gao and Ling-Ling Chen complexes and folates) are good start- ing points for finding novel antioxidant In his recent Opinion article (A new fact, the development of Mn(II)-containing drugs. perspective on radiation resistance based catalytic antioxidant drugs has attracted Hong-Yu Zhang is at the Institute of Bioinformatics and 5 on Deinococcus radiodurans. Nature Rev. much attention in recent years . However, National Key Laboratory of Crop Genetic Improvement, Microbiol. 7, 237–245 (2009))1, Michael as D. radiodurans contains a large number College of Life Science and Technology, Huazhong Daly proposes that high levels of manganese of metabolites, we speculate that other Agricultural University, Wuhan 430070, P. R. China. can protect proteins from the reactive compounds might also be responsible for the Xue-Juan Li, Na Gao and Ling-Ling Chen are at the oxygen species (ROS) that are produced antioxidant defence of D. radiodurans. Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Center for Advanced Study, during irradiation. Owing to the close link Through searching the Kyoto Shandong University of Technology, between reactive oxygen species and various Encyclopedia of Genes and Genomes Zibo 255049, P. R. China. diseases, there is continuing interest in find- (KEGG)6 and analysing the genome of Correspondence to H.Y.Z. 7 ing antioxidants as preventive or therapeutic D. radiodurans , the biosynthetic pathways e-mail: [email protected] drugs. According to the MDL Drug Data for some common antioxidant metabolites Report (MDDR)2, to date, seven antioxidant (for example, carotenoids, lipoic acid and 1. Daly, M. J. A new perspective on radiation resistance based on Deinococcus radiodurans. Nature Rev. drugs have been launched, most of which folates) could be identified. It is interesting Microbiol. 7, 237–245 (2009). (lipoic acid, policosanol, acetylcysteine, ide- to note that the mutant of D. radiodurans 2. MDL Drug Data Report (MDDR) (MDL Information Systems, San Leandro, 2004). benone and probucol) are directly or indi- that fails to synthesize carotenoids was more 3. Wang, P. & Schellhorn, H. E. Induction of resistance to rectly derived from natural antioxidants. sensitive to ionizing radiation and hydrogen hydrogen peroxide and radiation in Deinococcus radiodurans. Can. J. Microbiol. 41, 170–176 (1995). Exploring how organisms use antioxidants peroxide, and therefore that carotenoids, such 4. Makarova, K. S. et al. Genome of the extremely to combat ROS is therefore of great impor- as beta-carotene, lycopene and phytoene, radiation-resistant bacterium Deinococcus radiodurans viewed from the perspective of comparative genomics. tance for antioxidant drug discovery. indeed play an important part in the radiation Microbiol. Mol. Biol. Rev. 65, 44–79 (2001). It is well known that radiation-resistant resistance of D. radiodurans8. The antioxidant 5. Day, B. J. Catalytic antioxidants: a radical approach to new therapeutics. Drug Discov. Today 9, 557–566 bacteria have evolved strong antioxidant sys- and radioprotective powers of lipoic acid (2004). tems to survive ROS-mediated damage3. have been widely recognized9, which strongly 6. Kanehisa, M. & Goto, S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 28, 27–30 For example, various antioxidant enzymes, suggests that lipoic acid is also valuable in (2000). such as Mn- or Fe-superoxide dismutase, protecting D. radiodurans from oxidative 7. White, O. et al. Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1. Science 286, Cu/Zn-superoxide dismutase, catalase, per- damage. The radioprotective effect of folates 1571–1577 (1999). oxidase, thiol-alkyl hydroperoxide reductases, was also observed10, which was linked, at least 8. Tian, B., Xu, Z., Sun, Z., Lin, J. & Hua, Y. Evaluation of 10 the antioxidant effects of carotenoids from Deinococcus thioredoxin reductase, alkyl hydroperoxide in part, to the antioxidant activity of folates . radiodurans through targeted mutagenesis, reductase, peptide methionine sulphoxide Accumulating evidence indicates that folates chemiluminescence, and DNA damage analyses. Biochim. Biophys. Acta 1770, 902–911 (2007). reductase and glutaredoxin, have been are strong hydrogen and electron donors 9. Manda, K., Ueno, M., Moritake, T. & Anzai, K. α-Lipoic identified from Deinococcus radiodurans, one (when the proton is dissociated)11, especially acid attenuates X-irradiation-induced oxidative stress 3,4 in mice. Cell Biol. Toxicol. 23, 129–137 (2007). of the most radiation-resistant bacteria . in their reduced forms (for example, tetrahy- 10. Pote, M. S., Gandhi, N. M. & Mishra, K. P. Interestingly, Michael Daly revealed that non- drofolates), which endows them with sub- Antiatherogenic and radioprotective role of folic acid in whole body gamma-irradiated mice. Mol. Cell enzymic Mn(II) complexes also have a crucial stantial antioxidant potential that is similar Biochem. 292, 19–25 (2006). role in the antioxidant defence of D. radio- to that of α-tocopherol and ascorbic acid12. 11. Shen, L., Zhang, H.-Y. & Ji, H.-F. A thermodynamic 1 investigation of DPPH radical-scavenging mechanisms durans , which highlights the importance Moreover, the in vivo antioxidant effects of of folates. J. Mol. Struct. (Theochem) 856, 119–123 of small-molecule antioxidants in radiation folates have been preliminarily recognized, (2008). 12. Gliszczyńska-ńwigło, A. Folates as antioxidants. Food resistance. This finding not only sheds new which is independent of their well-known Chem. 101, 1480–1483 (2007). light on the radiation-resistant mechanisms benefits to reduce homocysteine13. Thus, it is 13. Doshi, S. N. et al. Folate improves endothelial function in coronary artery disease: an effect mediated by of D. radiodurans but also has direct implica- reasonable to infer that folates are involved in reduction of intracellular superoxide? Arterioscler. tions for antioxidant drug discovery. In the antioxidant defence of D. radiodurans. Thromb. Vasc. Biol. 21, 1196–1202 (2001). NATURE REVIEWS | MICROBIOLOGY www.nature.com/reviews/micro © 2009 Macmillan Publishers Limited. All rights reserved.
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