Biodiversity Research Center, Academia Sinica, 128 Academia Road Section 2, Nankang, Taipei 115, Taiwan; Department of Life Science, National Taiwan Normal University, Taipei 106, Taiwan; Biodiversity Program, Taiwan International Graduate Program, Academia Sinica and National Taiwan Normal University, Taipei 115, Taiwan.
Graduate Institute of Environmental Engineering, National Taiwan University, Taipei 106, Taiwan.
Cell Chem Biol. 2017 Jun 22;24(6):712-724.e7. doi: 10.1016/j.chembiol.2017.05.012. Epub 2017 May 25.
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 17β-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 wastewater treatment plants and two suburban rivers in Taiwan. The results significantly expand our understanding of microbial degradation of aromatic steroids at molecular level.
雌激素已被世界卫生组织列为第 1 组致癌物质，鉴于它们存在于世界各地的地表水，且长期暴露于受雌激素污染的水中会破坏动物的性发育，因此令人严重关切。迄今为止，雌激素代谢酶和基因仍然未知。使用分层功能基因组学方法，我们在 Sphingomonas sp. strain KC8 中鉴定出三个雌激素代谢基因簇。我们鉴定出几种雌酮衍生化合物，包括 4-羟基雌酮，一种间位裂解产物，和吡啶雌酮酸。基于酵母的雌激素测定表明，吡啶雌酮酸表现出可忽略不计的雌激素活性。我们对负责雌激素 A 环 17-脱氢和间位裂解的 17β-雌二醇脱氢酶和 4-羟基雌酮 4,5-加双氧酶进行了表征。在从台湾的两个污水处理厂和两个郊区河流采集的雌酮加标样本中检测到特征性的吡啶雌酮酸。研究结果极大地扩展了我们对微生物降解芳香甾族化合物的分子水平的认识。
