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.

近年来，微量成分的广泛存在及其对环境的影响越来越受到人们的关注。一类重要的微量成分是具有药用活性的化合物。越来越多的证据表明，长期接触具有药用活性的化合物，即使浓度极低，也可能对生态系统产生不利影响，例如胚胎发育受损、鱼类的摄食和社会行为改变、藻类生长受到抑制和呼吸作用减少。虽然其中一些影响是可逆的，但其他解剖、生理和基因的改变是永久性的。因此，评估、理解和减轻药物活性化合物和更广泛的微成分对环境的有害影响是环境工程和科学界面临的巨大挑战之一。目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制基础，因此无法明确指出在去除药物活性化合物中起作用的主要微生物群落和代谢途径。这导致对活性物种和临界衰减过程的身份缺乏共识。为了解开复杂性和位点特异性结果的难题，pi提出了一种理解药物活性化合物命运的基本方法——一种可以指导未来研究和实施工作的方法。本项目旨在对活性污泥中负责药物活性化合物转化和去除的微生物“活性组分”有一个清晰的认识，并阐明其组成代谢途径。第二个目标是量化和区分生长相关（与合成代谢有关）和非生长相关（与分解代谢或偶然反应有关）药物活性化合物的转化和降解。了解微生物过程对新出现的污染物的相互作用对于满足水质研究人员和专业人员目前面临的科学挑战至关重要。在拟议的研究中提供的理解这些过程的方法可能为未来的科学研究提供种子，旨在理解整个环境中的生物降解机制。低浓度环境中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。有效的废水处理对保持水质至关重要，但传统上认为有效的可能还需要包括微成分-这些设施从未专门设计用于处理的化合物。本研究将进一步发展和应用先进的微生物生态学技术，以揭示活性污泥中的细菌如何与药物活性化合物相互作用。这些先进的分子工具可以扩展到询问不同活性污泥配置中的药物活性化合物代谢。此外，对“活性组分”和代谢途径的了解可以帮助改进标准化方案，这些方案可以用于未来的研究，以估计现有的生物动力学参数，并构建更准确的药物活性化合物去除预测模型。从基本的角度来看，迄今为止还没有代谢模型可以描述药物活性化合物的降解途径。这可能是由于缺乏与理解药物活性化合物在混合细菌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建议开发并参数化这样一个模型。