Confirmation of Frm2 as a novel nitroreductase in Saccharomyces cerevisiae.
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.
Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
Seo Young
SY
Bang
Jeong Hoon
JH
Kim
Phil Young
PY
Lee
Kwang-Hee
KH
Bae
Jong Suk
JS
Lee
Pan-Soo
PS
Kim
Do Hee
DH
Lee
Pyung Keun
PK
Myung
Byoung Chul
BC
Park
Sung Goo
SG
Park
D015112:4-Nitroquinoline-1-oxide / Q000737:chemistry / Q000378:metabolism; D000634:Aminoquinolines / Q000737:chemistry / Q000378:metabolism; D000655:Amodiaquine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D002853:Chromatography, Liquid; D003001:Cloning, Molecular; D013058:Mass Spectrometry; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D009601:Nitroreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D015363:Quinolones / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C120195:4-nitroquinolone-1-oxide; C094707:7-chloro-4-(4'-hydroxy-3'-(2''-(ethylamino)ethanol)methylanilino)quinoline; D000634:Aminoquinolines; D015363:Quinolones; D029701:Saccharomyces cerevisiae Proteins; D009243:NAD; D000655:Amodiaquine; C001919:4-aminoquinoline-1-oxide; D015112:4-Nitroquinoline-1-oxide; C548067:FRM2 protein, S cerevisiae; D009601:Nitroreductases