Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf, Switzerland.
Environ Sci Technol. 2010 Sep 1;44(17):6628-35. doi: 10.1021/es101035b.
Partial microbial degradation of xenobiotic compounds in wastewater treatment plants (WWTPs) results in the formation of transformation products, which have been shown to be released and detectable in surface waters. Rule-based systems to predict the structures of microbial transformation products often fail to discriminate between alternate transformation pathways because structural influences on enzyme-catalyzed reactions in complex environmental systems are not well understood. The amide functional group is one such common substructure of xenobiotic compounds that may be transformed through alternate transformation pathways. The objective of this work was to generate a self-consistent set of biotransformation data for amide-containing compounds and to develop a metabolic logic that describes the preferred biotransformation pathways of these compounds as a function of structural and electronic descriptors. We generated transformation products of 30 amide-containing compounds in sludge-seeded bioreactors and identified them by means of HPLC-linear ion trap-orbitrap mass spectrometry. Observed biotransformation reactions included amide hydrolysis and N-dealkylation, hydroxylation, oxidation, ester hydrolysis, dehalogenation, nitro reduction, and glutathione conjugation. Structure-based interpretation of the results allowed for identification of preferences in biotransformation pathways of amides: primary amides hydrolyzed rapidly; secondary amides hydrolyzed at rates influenced by steric effects; tertiary amides were N-dealkylated unless specific structural moieties were present that supported other more readily enzyme-catalyzed reactions. The results allowed for the derivation of a metabolic logic that could be used to refine rule-based biotransformation pathway prediction systems to more specifically predict biotransformations of amide-containing compounds.
废水处理厂（WWTPs）中异生物质的部分微生物降解会导致转化产物的形成，这些转化产物已被证明会释放到地表水中并被检测到。用于预测微生物转化产物结构的基于规则的系统往往无法区分替代转化途径，因为复杂环境系统中酶促反应的结构影响尚未得到很好的理解。酰胺官能团是异生物质中常见的亚结构之一，可能通过替代转化途径发生转化。这项工作的目的是生成一组包含酰胺化合物的自洽生物转化数据，并开发一种代谢逻辑，该逻辑将这些化合物的首选生物转化途径描述为结构和电子描述符的函数。我们在接种污泥的生物反应器中生成了 30 种含酰胺化合物的转化产物，并通过 HPLC-线性离子阱-轨道阱质谱法对其进行了鉴定。观察到的生物转化反应包括酰胺水解和 N-脱烷基化、羟化、氧化、酯水解、脱卤化、硝基还原和谷胱甘肽结合。基于结构的结果解释允许确定酰胺生物转化途径的偏好：伯酰胺迅速水解；仲酰胺的水解速率受空间效应影响；叔酰胺会发生 N-脱烷基化，除非存在特定的结构部分，否则这些结构部分支持其他更容易被酶催化的反应。该结果允许推导出一种代谢逻辑，可以用于改进基于规则的生物转化途径预测系统，以更具体地预测含酰胺化合物的生物转化。
