A Metagenomic Approach to the Identification of UDP-Glucose 4-Epimerase as a Menadione Resistance Protein

Quinones are potentially toxic agents that generate reactive oxygen species (ROS) upon reduction. We screened a metagenomic library for a menadione resistance gene to identify UDP-glucose 4-epimerase (UGE). Escherichia coli carrying the gene became resistant to various quinones, but not to ROS. Because UGE is involved in the biosynthesis of lipopolysaccharides, it may have contributed to forming a permeability barrier against lipophilic quinones.

[1]  Nico P E Vermeulen,et al.  Enzyme-Catalyzed Activation of Anticancer Prodrugs , 2004, Pharmacological Reviews.

[2]  V. Korolik,et al.  The galE Gene of Campylobacter jejuni Is Involved in Lipopolysaccharide Synthesis and Virulence , 2000, Infection and Immunity.

[3]  H. Suenaga,et al.  Functional screening of a metagenomic library for genes involved in microbial degradation of aromatic compounds. , 2007, Environmental microbiology.

[4]  S. Farr,et al.  Oxidative stress responses in Escherichia coli and Salmonella typhimurium. , 1991, Microbiological reviews.

[5]  J. Tiedje,et al.  DNA recovery from soils of diverse composition , 1996, Applied and environmental microbiology.

[6]  V. C. Stamoudis,et al.  Determination of biological removal of organic constituents in quench waters from high-BTU coal-gasification pilot plants , 1980 .

[7]  P. Frey,et al.  Molecular structure of the NADH/UDP-glucose abortive complex of UDP-galactose 4-epimerase from Escherichia coli: implications for the catalytic mechanism. , 1996, Biochemistry.

[8]  J. Bolton,et al.  Role of quinones in toxicology. , 2000, Chemical research in toxicology.

[9]  Dick B Janssen,et al.  Efficient recovery of environmental DNA for expression cloning by indirect extraction methods. , 2003, FEMS microbiology ecology.

[10]  F. Borges,et al.  Identification of Streptococcus thermophilus CNRZ368 Genes Involved in Defense against Superoxide Stress , 2004, Applied and Environmental Microbiology.

[11]  J. Handelsman,et al.  Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products. , 1998, Chemistry & biology.

[12]  A. Thibessard,et al.  Effects of rodA and pbp2b Disruption on Cell Morphology and Oxidative Stress Response of Streptococcus thermophilus CNRZ368 , 2002, Journal of bacteriology.

[13]  M. Vaara.  Outer membrane permeability barrier to azithromycin, clarithromycin, and roxithromycin in gram-negative enteric bacteria , 1993, Antimicrobial Agents and Chemotherapy.