Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 510632, China.
Guangdong Ocean Engineering Technology School, Guangzhou, 510320, China.
J Hazard Mater. 2020 Apr 15;388:121737. doi: 10.1016/j.jhazmat.2019.121737. Epub 2019 Nov 21.
Although bisphenol A (BPA) can be transformed by CYP450, the metabolic networks involved in regulating the transformation processes are not clear. In this study, Escherichia coli harboring the gene encoding CYP450 was used as a model to elucidate the BPA degradation pathway and the associated metabolic network using a proteomic approach. The results showed that CYP450 promotes the transformation of BPA, generating 1,2-bis(4-hydroxyphenyl)-2-propanol and 2,2-bis(4-hydroxyphenyl)-1-propanol, with hydroquinone and 4-(2-hydroxypropan-2-yl)phenol formed in another pathway. The DNA adducts formed by 1,4-benzoquinone were reduced, and CYP450 played a positive role in cellular homeostasis by promoting the transformation of BPA and mismatch repair. An increase in the synthesis of cell membrane lipids was observed after dislodging BPA. BPA disturbed folate metabolism by decreasing the abundance of dihydrofolate reductase, which inhibited microbial metabolism in the absence of CYP450. The findings of this study revealed the molecular mechanism associated with the metabolic network responsible for pollutant tolerance and degradation.
尽管双酚 A（BPA）可以被 CYP450 转化，但调节转化过程的代谢网络尚不清楚。在这项研究中，使用含有 CYP450 编码基因的大肠杆菌作为模型，通过蛋白质组学方法阐明 BPA 降解途径和相关代谢网络。结果表明，CYP450 促进 BPA 的转化，生成 1,2-双（4-羟基苯基）-2-丙醇和 2,2-双（4-羟基苯基）-1-丙醇，另一条途径生成对苯二酚和 4-（2-羟基丙基）苯酚。1,4-苯醌形成的 DNA 加合物被还原，CYP450 通过促进 BPA 的转化和错配修复，在细胞内稳态中发挥积极作用。BPA 被排出后，细胞膜脂质的合成增加。BPA 通过降低二氢叶酸还原酶的丰度来干扰叶酸代谢，从而在没有 CYP450 的情况下抑制微生物代谢。本研究的结果揭示了与污染物耐受和降解相关的代谢网络的分子机制。
