Confirmation of Frm2 as a novel nitroreductase in Saccharomyces cerevisiae

• Published in: Biochemical and biophysical research communications Vol. 423; no. 4; pp. 638 - 641
• Main Authors: Bang, Seo Young, Kim, Jeong Hoon, Lee, Phil Young, Bae, Kwang-Hee, Lee, Jong Suk, Kim, Pan-Soo, Lee, Do Hee, Myung, Pyung Keun, Park, Byoung Chul, Park, Sung Goo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.07.2012
• Subjects: 4-AQO; 4-Nitroquinoline-1-oxide - chemistry; 4-Nitroquinoline-1-oxide - metabolism; 4-NQO; Aminoquinolines - chemistry; Aminoquinolines - metabolism; Amodiaquine - analogs & derivatives; Amodiaquine - chemistry; Amodiaquine - metabolism; Chromatography, Liquid; Cloning, Molecular; Frm2; Mass Spectrometry; NAD - chemistry; NAD - metabolism; Nitroreductase; Nitroreductases - chemistry; Nitroreductases - genetics; Nitroreductases - metabolism; Oxidative Stress; Quinolones - chemistry; Quinolones - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Frm2; 4-NQO; Oxidative stress; 4-AQO; LC–MS; Nitroreductase; 4-NOSO
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.05.156

► We measured the nitroreductase activity of Frm2 on 4-NQO. ► We confirmed for the first time that Frm2 is a novel nitroreductase. ► We demonstrated its involvement in the oxidative stress defense system. Nitroreductases comprise a group of FMN- or FAD-dependent enzymes that reduce nitrosubstituted compounds by using NAD(P)H, and are found in bacterial species and yeast. Although there is little information on the biological functions of nitroreductases, some studies suggest their possible involvement in oxidative stress responses. In the yeast Saccharomyces cerevisiae, a putative nitroreductase protein, Frm2, has been identified based on its sequence similarity with known bacterial nitroreductases. Frm2 has been reported to function in the lipid signaling pathway. To study the functions of Frm2, we measured the nitroreductase activity of purified Frm2 on 4-nitroquinoline-N-oxide (4-NQO) using NADH. LC-MS analysis of the reaction products revealed that Frm2 reduced NQO into 4-aminoquinoline-N-oxide (4-AQO) via 4-hydroxyaminoquinoline (4-HAQO). An Frm2 deletion mutant exhibited growth inhibition in the presence of 4-NQO. Thus, in this study, we demonstrate a novel nitroreductase activity of Frm2 and its involvement in the oxidative stress defense system.