Zhao Mei-Ai, Gu Hao, Zhang Chuan-Jie, Jeong In-Hong, Kim Jeong-Han, Zhu Yong-Zhe
College of Life Sciences, Qingdao Agricultural University Changcheng Rd, Chengyang Qingdao City Shandong Province 266-109 China.
College of Chemistry and Pharmacy, Qingdao Agricultural University Changcheng Rd, Chengyang Qingdao City Shandong Province 266-109 China
RSC Adv. 2020 May 26;10(33):19659-19668. doi: 10.1039/d0ra02253e. eCollection 2020 May 20.
The fungal metabolism of diazinon was investigated and the microbial model ( ATCC36112) could effectively degrade the organophosphorus pesticide (diazinon) mediated by cytochrome P450, which was mainly involved in oxidation and hydrolysis of phase I metabolism. Approximately 89% of diazinon was removed within 7 days and was not observed after 13 days with concomitant accumulation of eight metabolites. Structures of the metabolites were fully or tentatively identified with GC-MS and H, C NMR. The major metabolites of diazinon were diethyl (2-isopropyl-6-methylpyrimidin-4-yl) phosphate (diazoxon) and 2-isopropyl-6-methyl-4-pyrimidinol (pyrimidinol), and formation of minor metabolites was primarily the result of hydroxylation. To determine the responsible enzymes in diazinon metabolism, piperonyl butoxide and methimazole were treated, and the kinetic responses of diazinon and its metabolites by were measured. Results indirectly demonstrated that cytochrome P450 and flavin monooxygenase were involved in the metabolism of diazinon, but methimazole inhibited the metabolism less effectively. Based on the metabolic profiling, a possible metabolic pathway involved in phase I metabolism of diazinon was proposed, which would contribute to providing insight into understanding the toxicological effects of diazinon and the potential application of fungi on organophosphorus pesticides.
研究了二嗪农的真菌代谢情况,微生物模型(ATCC36112)能够在细胞色素P450介导下有效降解有机磷农药(二嗪农),细胞色素P450主要参与I相代谢的氧化和水解过程。约89%的二嗪农在7天内被去除,13天后未观察到二嗪农,同时积累了8种代谢产物。通过气相色谱 - 质谱联用仪(GC-MS)和氢、碳核磁共振波谱(H,C NMR)对代谢产物的结构进行了完全或初步鉴定。二嗪农的主要代谢产物是二乙基(2 - 异丙基 - 6 - 甲基嘧啶 - 4 - 基)磷酸酯(二嗪磷)和2 - 异丙基 - 6 - 甲基 - 4 - 嘧啶醇(嘧啶醇),次要代谢产物的形成主要是羟基化的结果。为了确定二嗪农代谢过程中的相关酶,用胡椒基丁醚和甲巯咪唑进行处理,并测定了二嗪农及其代谢产物的动力学响应。结果间接表明细胞色素P450和黄素单加氧酶参与了二嗪农的代谢,但甲巯咪唑对代谢的抑制作用较弱。基于代谢谱,提出了二嗪农I相代谢可能的代谢途径,这将有助于深入了解二嗪农的毒理学效应以及真菌在有机磷农药方面的潜在应用。