Role of UDP-Glycosyltransferase (ugt) Genes in Detoxification and Glycosylation of 1-Hydroxyphenazine (1-HP) in Caenorhabditis elegans,Chemical Research in Toxicology

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Role of UDP-Glycosyltransferase (ugt) Genes in Detoxification and Glycosylation of 1-Hydroxyphenazine (1-HP) in Caenorhabditis elegans
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2024-03-15 , DOI: 10.1021/acs.chemrestox.3c00410
Muhammad Zaka Asif _{1,

2} , Kelsey A Nocilla ₂ , Li Ngo ₂ , Man Shah ₂ , Yosef Smadi ₂ , Zaki Hafeez ₂ , Michael Parnes ₂ , Allie Manson ₂ , John N Glushka ₂ , Franklin E Leach _{2,

3} , Arthur S Edison _{1,

2,

4}

Affiliation

Caenorhabditis elegans 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 Pseudomonas aeruginosa, kills C. elegans. We previously showed that C. elegans detoxifies 1-HP by adding one, two, or three glucose molecules in N2 worms. Our current study evaluates the roles that some UDP-glycosyltransferase (ugt) genes play in 1-HP detoxification. We show that ugt-23 and ugt-49 knockout mutants are more sensitive to 1-HP than reference strains N2 or PD1074. Our data also show that ugt-23 knockout mutants produce reduced amounts of the trisaccharide sugars, while the ugt-49 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 C. elegans and showed that one of the sugar modifications contains an N-acetylglucosamine (GlcNAc) in place of glucose. This implies broad specificity regarding UGT function and the role of genes other than ogt-1 in adding GlcNAc, at least in small-molecule detoxification.

中文翻译：

UDP-糖基转移酶 (ugt) 基因在秀丽隐杆线虫 1-羟基吩嗪 (1-HP) 解毒和糖基化中的作用

秀丽隐杆线虫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型生物，但第二阶段解毒机制尚未得到充分研究。 1-羟基吩嗪 (1-HP) 是一种由铜绿假单胞菌产生的毒素，可杀死秀丽隐杆线虫。我们之前表明，秀丽隐杆线虫通过在 N2 蠕虫中添加一个、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 UDP-糖基转移酶 ( ugt ) 基因在 1-HP 解毒中的作用。我们发现ugt-23和ugt-49敲除突变体对 1-HP 比参考菌株 N2 或 PD1074 更敏感。我们的数据还表明，与参考菌株相比， ugt-23敲除突变体产生的三糖量减少，而ugt-49敲除突变体产生的所有 1-HP 衍生物（吡喃葡萄糖基产物除外）的量减少。我们表征了由秀丽隐杆线虫产生的三糖吩嗪的结构，并表明其中一种糖修饰包含N-乙酰氨基葡萄糖 (GlcNAc) 代替葡萄糖。这意味着 UGT 功能和除OGT-1以外的基因在添加 GlcNAc 中的作用（至少在小分子解毒中）具有广泛的特异性。

更新日期：2024-03-15

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