Collaborative Research: Probing Active Fraction and Metabolic Function to Elucidate Mechanisms of Pharmaceutical Biotransformations during Nitrification-Denitrification

合作研究：探索活性组分和代谢功能以阐明硝化反硝化过程中药物生物转化的机制

• 批准号: 1438578
• 负责人: Kartik Chandran
• 金额: $ 16.5万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1438578&HistoricalAwards=false
• 关键词: Collaborative; Research; Probing; Active; Fraction

1438578Chandran1438221RamsburgThe widespread occurrence and environmental impacts of microconstituents has received increasing attention in recent years. An important class of microconstituents is pharmaceutically active compounds. There is a growing body of evidence that suggests chronic exposure to pharmaceutically active compounds, even at extremely low concentrations could have adverse effects on ecosystems, such as impaired embryo development, modified feeding and social behavior of fish, suppression of growth and reduction in respiration in algae. While some of these effects are reversible, other anatomical, physiological, and genetic alterations are permanent. Thus, the challenge of assessing, understanding, and mitigating the deleterious influence of pharmaceutically active compounds, and microconstituents more broadly, on the environment is one of the great challenges facing the environmental engineering and science community. Current approaches to study pharmaceutically active compounds fate in biological wastewater treatment generally lack a mechanistic basis and therefore cannot unambiguously pinpoint the protagonist microbial communities and metabolic pathways that are active in the removal of pharmaceutically active compounds. This leads to a lack of consensus regarding the identity of active species and critical attenuation processes. To unravel the conundrum of complexity and site specific results, the PIs propose a fundamental approach to understanding the fate of pharmaceutically active compounds - one that can guide future research and implementation efforts. This project aims to develop a clear understanding of the microbial "active fraction" in activated sludge which is responsible for the transformation and removal of pharmaceutically active compounds, and to elucidate the constituent metabolic pathways. A secondary objective is to quantify and differentiate between growth associated (linked to anabolism) and non-growth associated (linked to catabolism or fortuitous reactions) pharmaceutically active compounds transformation and degradation. Understanding the interplay of microbial processes acting on contaminants of emerging concern is critical to meeting the scientific challenges now facing water quality researchers and professionals. The approach to understanding these processes offered in the proposed research may seed future scientific investigations aimed at understanding biodegradation mechanisms throughout the environment.The influence of anthropogenic chemical mixtures present within the environment at low concentration is one of the great challenges facing scientists and engineers in the 21st century. Effective wastewater treatment is critical to maintaining water quality, but what is traditionally thought of as effective may need to also include microconstituents - compounds that these facilities were never specifically designed to treat. This study will further the development and application of advanced microbial-ecological techniques to shed new light on how bacteria within activated sludge interact with pharmaceutically active compounds. The advanced understanding enabled by these state-of-the-art molecular tools can be extended to interrogate pharmaceutically active compound metabolism in different activated sludge configurations. Further, the knowledge of the "active fraction" and metabolic pathways can help improve standardized protocols that can be used by future studies to estimate the extant biokinetic parameters and to construct more accurate predictive models for pharmaceutically active compounds removal. From a fundamental perspective, there is no metabolic model to date, that can describe pharmaceutically active compounds degradation pathways. This is possibly due to a lack of detailed studies related to understanding the mechanisms by which pharmaceutically active compounds are biodegraded within mixed communities of bacteria. As part of this project, the PIs propose to develop and parameterize such a model.

1438578CHANDRAN1438221RAMSBURGTHE近年来，微生物的广泛发生和环境影响受到了越来越多的关注。一类重要的微晶体是药物活性化合物。越来越多的证据表明，即使在极低的浓度下，长期暴露于药物活性的化合物也可能对生态系统产生不利影响，例如胚胎发育受损，鱼类的改良喂养和社会行为，抑制鱼类的生长以及藻类呼吸的减少。尽管其中一些作用是可逆的，但其他解剖学，生理和遗传改变是永久性的。因此，评估，理解和减轻药物活性化合物的有害影响以及更广泛的环境的挑战是环境工程和科学界面临的重大挑战之一。当前研究生物废水处理中药物活性化合物命运的方法通常缺乏机械基础，因此不能明确地指出主动性微生物群落和代谢途径，这些群落和代谢途径活跃于去除药物活性化合物时。这导致关于活性物种的身份和关键衰减过程缺乏共识。为了揭示复杂性和特定现场结果的难题，PI提出了一种理解药物活跃化合物的命运的基本方法 - 可以指导未来的研究和实施工作。该项目旨在对活性污泥中的微生物“活性分数”有清晰的了解，该污泥负责转化和去除药物活性化合物，并阐明成分代谢途径。次要目标是量化和区分相关的生长（与合成代谢相关）和相关的非增长（与分解代谢或偶然反应有关）药物具有活性化合物的转化和降解。了解对新兴关注的污染物的微生物过程的相互作用对于应对现在水质研究人员和专业人士面临的科学挑战至关重要。理解拟议研究中提供的这些过程的方法可能播种旨在理解整个环境中生物降解机制的未来科学研究。在低浓度下，环境中存在的人为化学混合物的影响是21世纪科学家和工程师面临的巨大挑战之一。有效的废水处理对于维持水质至关重要，但是传统上认为有效的东西可能还需要包括微质量 - 这些设施从未专门设计用于治疗的化合物。这项研究将进一步开发和应用高级微生物生态技术，以解散活性污泥中的细菌如何与药物活性化合物相互作用。这些最先进的分子工具能够扩展这些先进的理解，以在不同的活性污泥构型中询问药物活跃的复合代谢。此外，对“主动分数”和代谢途径的知识可以帮助改善标准化方案，这些方案可以通过未来的研究使用来估计现有的生物动力学参数，并构建用于去除药物活性化合物的更准确的预测模型。从基本的角度来看，迄今为止没有代谢模型可以描述药物活性化合物降解途径。这可能是由于缺乏与了解在细菌混合群落中生物降解的机制相关的详细研究。作为该项目的一部分，PI提议开发和参数化此类模型。