迪尼克尔酶的进化是为了代谢制药甲福明及其对废水和人类微生物的影响
Lambros J Tassoulas1,2, Joel A Rankin1,2, Mikael H Elias1,2
1Department of Biochemistry, Biophysics, and Molecular Biology, University of Minnesota, Minneapolis, MN 55455.
概括
研究人员确定了两种基因,mfmA和mfmB,它们负责废水中分解常见的糖尿病药物甲胺. 这一发现揭示了一种广泛存在的微生物酶,对环境中的甲胺降解至关重要.
科学领域:
- 环境微生物学 环境微生物学
- 生物化学 生物化学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 甲胺是二型糖尿病的一线药物,是广泛存在的环境污染物.
- 它的环境命运和微生物降解途径,特别是涉及的基因,仍然在很大程度上没有特征.
研究的目的:
- 为了识别和描述负责废水中甲胺分解的基因和酶.
- 阐明通过微生物酶进行甲胺水解的生化机制和结构基础.
主要方法:
- 从能够降解甲胺的活性污泥中分离细菌.
- 基因克隆,表达和净化甲胺降解复合体 (MfmAB).
- 生物化学测试以确定酶动力学和基质特异性.
- 进行X射线晶体学以确定MfmAB复合体的结构.
- 部位定向突变发生,以确定关键的活性部位残留物.
主要成果:
- 确定了两种基因,mfmA和mfmB,它们编码了一个依赖的尿素酶复合体 (MfmAB).
- MfmAB有效地将甲福胺化为二甲基胺和氨酸 (kcat/KM = 9.6 × 10^3 M^-1s^-1).
- 晶体结构揭示了在MfmA活性位点协调的离子,这对催化至关重要.
- 突变性研究确切地指出了对甲胺水解必不可少的关键残留物.
- 在全球的污水处理厂中发现了mfmAB基因,这表明其分布广泛.
结论:
- 酶复合体MfmAB负责废水中的甲福林的微生物分解.
- 这种依赖的化酶对甲胺具有很高的特异性.
- 由于mfmAB基因的广泛存在,这表明在环境中有重要的微生物途径用于甲胺修复.
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