Asif Muhammad Zaka, Nocilla Kelsey A, Ngo Li, Shah Man, Smadi Yosef, Hafeez Zaki, Parnes Michael, Manson Allie, Glushka John N, Leach Franklin E, Edison Arthur S
Department of Biochemistry & Molecular Biology, University of Georgia, Athens, Georgia 30602, United States.
Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.
Chem Res Toxicol. 2024 Apr 15;37(4):590-599. doi: 10.1021/acs.chemrestox.3c00410. Epub 2024 Mar 15.
is a useful model organism to study the xenobiotic detoxification pathways of various natural and synthetic toxins, but the mechanisms of phase II detoxification are understudied. 1-Hydroxyphenazine (1-HP), a toxin produced by the bacterium , kills . We previously showed that detoxifies 1-HP by adding one, two, or three glucose molecules in N2 worms. Our current study evaluates the roles that some UDP-glycosyltransferase () genes play in 1-HP detoxification. We show that and knockout mutants are more sensitive to 1-HP than reference strains N2 or PD1074. Our data also show that knockout mutants produce reduced amounts of the trisaccharide sugars, while the knockout mutants produce reduced amounts of all 1-HP derivatives except for the glucopyranosyl product compared to the reference strains. We characterized the structure of the trisaccharide sugar phenazines made by and showed that one of the sugar modifications contains an -acetylglucosamine (GlcNAc) in place of glucose. This implies broad specificity regarding UGT function and the role of genes other than in adding GlcNAc, at least in small-molecule detoxification.
是研究各种天然和合成毒素的异生物质解毒途径的有用模式生物,但II期解毒机制的研究较少。1-羟基吩嗪(1-HP)是由细菌产生的一种毒素,可杀死。我们之前表明,在N2蠕虫中通过添加一个、两个或三个葡萄糖分子来解毒1-HP。我们目前的研究评估了一些尿苷二磷酸糖基转移酶()基因在1-HP解毒中的作用。我们表明,与参考菌株N2或PD1074相比,和敲除突变体对1-HP更敏感。我们的数据还表明,与参考菌株相比,敲除突变体产生的三糖量减少,而敲除突变体除了吡喃葡萄糖基产物外,所有1-HP衍生物的产量都减少。我们对和产生的三糖吩嗪的结构进行了表征,并表明其中一种糖修饰含有N-乙酰葡糖胺(GlcNAc)代替葡萄糖。这意味着UGT功能具有广泛的特异性,并且除了在添加GlcNAc方面的作用外,至少在小分子解毒中,其他基因也发挥作用。