Biochemical Mechanisms and Catabolic Enzymes Involved in Bacterial Estrogen Degradation Pathways
Biochemical Mechanisms and Catabolic Enzymes Involved in Bacterial Estrogen Degradation Pathways
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DOI：
10.1016/j.chembiol.2017.05.012
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发表时间：
2017-06-22
影响因子：
8.6
通讯作者：
Chiang, Yin-Ru
中科院分区：
文献类型：
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作者：
Chen, Yi-Lung;Yu, Chang-Ping;Chiang, Yin-Ru
雌激素已被世界卫生组织归类为第一类致癌物质，鉴于它们存在于世界各地的地表水中，并且长期暴露在受雌激素污染的水中会扰乱动物的性发育，因此是一个令人严重关切的问题。到目前为止，雌激素分解代谢酶和基因仍不清楚。利用分级功能基因组学方法，我们在鞘氨醇单胞菌中鉴定了三个雌激素分解代谢基因簇。菌株KC8。我们鉴定了几种雌酮类化合物，包括4-羟基雌酮，一种间切产物，以及吡啶雌酮酸。以酵母为基础的雌激素测定表明，吡啶雌酮酸的雌激素活性可以忽略不计。我们鉴定了17β-雌二醇脱氢酶和4-羟雌酮4，5-双加氧酶，它们分别负责雌激素A环的17-脱氢和异位裂解。从台湾两个污水处理厂和两条郊区河流采集的雌酮添加样本中，检测到了特征的吡啶雌酮酸。这些结果极大地扩展了我们在分子水平上对芳香类固醇微生物降解的理解。
Estrogens have been classified as group 1 carcinogens by the World Health Organization and represent a significant concern given that they are found in surface waters worldwide, and long-term exposure to estrogen-contaminated water can disrupt sexual development in animals. To date, the estrogen catabolic enzymes and genes remain unknown. Using a tiered functional genomics approach, we identified three estrogen catabolic gene clusters in Sphingomonas sp. strain KC8. We identified several estrone-derived compounds, including 4-hydroxyestrone, a meta-cleavage product, and pyridinestrone acid. The yeast-based estrogen assay suggested that pyridinestrone acid exhibits negligible estrogenic activity. We characterized 17 beta-estradiol dehydrogenase and 4-hydroxyestrone 4,5-dioxygenase, responsible for the 17-dehydrogenation and meta-cleavage of the estrogen A ring, respectively. The characteristic pyridinestrone acid was detected in estrone-spiked samples collected from two waste-water treatment plants and two suburban rivers in Taiwan. The results significantly expand our understanding of microbial degradation of aromatic steroids at molecular level.